Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.

In the reported study we applied the targeted metabolomic profiling employing high pressure liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC–MS/MS) to understand the pathophysiology of gestational diabetes mellitus (GDM), early identification of women who are at risk of developing GDM, and the differences in recovery postpartum between these women and normoglycemic women. We profiled the peripheral blood from patients during the second trimester of pregnancy and three months, and one year postpartum. In the GDM group Arg, Gln, His, Met, Phe and Ser were downregulated with statistical significance in comparison to normoglycemic (NGT) women. From the analysis of the association of all amino acid profiles of GDM and NGT women, several statistical models predicting diabetic status were formulated and compared with the literature, with the arginine-based model as the most promising of the screened ones (area under the curve (AUC) = 0.749). Our research results have shed light on the critical role of arginine in the development of GDM and may help in precisely distinguishing between GDM and NGT and earlier detection of GDM but also in predicting women with the increased type 2 diabetes mellitus (T2DM) risk.

Extracts from the defatted evening primrose (Oenothera paradoxa Hudziok) seeds are the source of a range of stable polyphenolic compounds, including ellagic acid, gallic acid, and catechin. Our studies evaluate, for the first time, the influence of evening primrose isopropanol extract (EPE) on malignant pleural mesothelioma (MPM) cells. MPM is rarely diagnosed, its high aggressiveness and frequently noted chemoresistance limit its treatment schemes and it is characterized by low prognostic features. Here, we demonstrate that EPE inhibited MPM growth in a dose-dependent manner in cells with increased invasion properties. Moreover, EPE treatment resulted in cell cycle arrest in the G2/M phase and increased apoptosis in invasive MPM cell lines. Additionally, EPE strongly limited invasion and MMP-7 secretion in MPM cancer cells. Our original data provide evidence about the potential anti-invasive effects of EPE in MPM therapy treatment.

An efficient method for large laboratory scale synthesis of dinucleoside (3¢,5¢)-methylphosphonothioates and their methylphosphonoselenoate congeners is presented. Bis-(1,2,4-triazoloyl)methylphosphonite generated in situ from methyldichlorophosphine is used as a phosphitylating agent and the preparations are performed as one-pot-reactions without isolation of the reactive PIII intermediates.Oligonucleotides modified at preselected internucleotide linkages with methylphosphonate functions have become indispensable tools for studies of interactions between DNA and other biomolecules, such as DNA, RNA and proteins. 2 Since the aforementioned modifications by virtue of asymmetry of the phosphorus atom induce polydiastereomerism of the corresponding oligonucleotide constructs, the obvious consequence of their non-stereocontrolled synthesis is the separation of diastereomers and assignment of the sense of P-chirality before application of such modified oligonucleotide constructs in structural studies. An alternative and preferred approach to their synthesis relies upon the preparation of diastereomerically pure dinucleoside (3¢,5¢)-methylphosphonates (1, X = O) or methylphosphonothioates (2, X = S) either methylphosphonoselenoates (3, X = Se) and their use as dimeric building blocks in the solid-phase synthesis of chimeric oligonucleotides. Such an approach in the case of 1 has been successfully used for synthesis of the third generation of antisense agents, 3 as well as for construction of chimeric molecules useful for elucidation of contacts between DNA/RNA and proteins 4 or in the studies of DNA conformation and bending. 5 Dinucleoside methylphosphonoselenoates 3 incorporated into modified oligonucleotides can facilitate crystallization of DNA/RNA or DNA/protein complexes and simplify their X-ray structural analysis due to the MAD effect. 6 However, one of the serious limitations in such applications, despite numerous efforts of different groups, is insufficient availability of diastereomerically pure dinucleotides 1-3, mostly obtained by laborious synthetic procedures. 7 In this communication we present our results on the design of the large-scale synthesis of the aforementioned dinucleotides 2 and 3. The key step in our strategy involves either the sulfurization or selenization of the corresponding PIII intermediates, providing a set of new dinucleotide building blocks that enables the synthesis of chimeric oligonucleotides bearing methylphosphonothioate or methylphosphonoselenoate functions. In addition to the novelty of this phosphonoselenoate modification, both methylphosphonothioates 2 and methylphosphonoselenoate congeners 3 can be stereospecifically and almost quantitatively converted to the parent methylphosphonates 1 by simple treatment with Oxone ® . 6Conventional synthesis of dinucleotides 1 uses MePCl 2 (4) as the phosphitylating agent. 8 However, the use of this bifunctional phosphitylating agent due to its high reactivity and the lack of selectivity of both chlorines with different nucleoside compone...

The synthesis of protected model dinucleoside (3',5')‐O‐aryl phosphorothioates, their separation into pure diastereomers, and their successful incorporation into oligonucleotides followed by stereospecific deprotection of the O‐aryl phosphorothioate function with oximate ion (inversion) enables the preparation of chimeric PO/PS‐oligonucleotides with a predetermined sense of P‐chirality at each internucleotide phosphorothioate position. The absolute configuration at the phosphorus of the internucleotide O‐aryl phosphorothioate in “dimeric building blocks” has been assigned. The 3'‐terminal SP‐phosphorothioate linkages effectively protect such chimeric constructs from degradation by human plasma exonuclease (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)