Composition and structure of benzoilacetonates of transition metals and the possibility of their use as gaschromatographic sorbents

The aim of the work was to obtain and study chelate complexes of benzoylacetonates of transition metals, to study their chromatographic properties by the example of mesoporous silica gel modified with benzoylacetonates Co, Ni, Cu, and to establish a correlation between the composition, structure and properties of the materials obtained. To study the physicochemical properties of the complexes and sorbents obtained, modern equipment was used. The composition of the synthesized metal chelate complexes was studied by IR, atomic-emission spectroscopy, gravimetric and elemental analyzes. Chromatographic studies were performed on a gas chromatograph MAESTRO 7820 (Agilent Technologies) with a flame ionization detector. In this work we used metal filled columns 1 m long and inner diameter 3 mm. Results: Sorbents based on mesoporous silica gel modified by intracomplex compounds of benzoylacetonates of cobalt, nickel and copper were obtained. The parameters of gas-chromatographic retention of various classes of organic compounds are determined

Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4

MicroRNAs regulate the maladaptation of endothelial cells (ECs) to naturally occurring disturbed blood flow at arterial bifurcations resulting in arterial inflammation and atherosclerosis in response to hyperlipidemic stress. Here, we show that reduced endothelial expression of the RNAse Dicer, which generates almost all mature miRNAs, decreases monocyte adhesion, endothelial C-X-C motif chemokine 1 (CXCL1) expression, atherosclerosis and the lesional macrophage content in apolipoprotein E knockout mice (Apoe(-/-)) after exposure to a high-fat diet. Endothelial Dicer deficiency reduces the expression of unstable miRNAs, such as miR-103, and promotes Kruppel-like factor 4 (KLF4)-dependent gene expression in murine atherosclerotic arteries. MiR-103 mediated suppression of KLF4 increases monocyte adhesion to ECs by enhancing nuclear factor-kappa B-dependent CXCL1 expression. Inhibiting the interaction between miR-103 and KLF4 reduces atherosclerosis, lesional macrophage accumulation and endothelial CXCL1 expression. Overall, our study suggests that Dicer promotes endothelial maladaptation and atherosclerosis in part by miR103-mediated suppression of KLF4

Endothelial overexpression of TGF-β-induced protein impairs venous thrombus resolution

Endothelial cells play a critical role during venous thrombus remodeling, and unresolved, fibrotic thrombi with irregular vessels obstruct the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to identify endothelial mediators of impaired venous thrombus resolution and to determine their role in the pathogenesis of the vascular obstructions in patients with CTEPH. Endothelial cells outgrown from pulmonary endarterectomy specimens (PEA) were processed for mRNA profiling, and nCounter gene expression and immunohistochemistry analysis of PEA tissue microarrays and immunoassays of plasma were used to validate the expression in CTEPH. Lentiviral overexpression in human pulmonary artery endothelial cells (HPAECs) and exogenous administration of the recombinant protein into C57BL/6J mice after inferior Vena cava ligation were employed to assess their role for venous thrombus resolution. RT2 PCR profiler analysis demonstrated the significant overexpression of factors downstream of transforming growth factor beta (TGFβ), that is TGFβ-Induced Protein (TGFBI or BIGH3) and transgelin (TAGLN), or involved in TGFβ signaling, that is follistatin-like 3 (FSTL3) and stanniocalcin-2 (STC2). Gene expression and immunohistochemistry analysis of tissue microarrays localized potential disease candidates to vessel-rich regions. Lentiviral overexpression of TGFBI in HPAECs increased fibrotic remodeling of human blood clots in vitro, and exogenous administration of recombinant TGFBI in mice delayed venous thrombus resolution. Significantly elevated plasma TGFBI levels were observed in patients with CTEPH and decreased after PEA. Our findings suggest that overexpression of TGFBI in endothelial promotes venous thrombus non-resolution and fibrosis and is causally involved in the pathophysiology of CTEPH

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Влияние исходного структурно-фазового состояния низкоуглеродистых малолегированных сталей на формирование структуры и свойств лазерных сварных соединений

В результате комплексных структурных исследований показано, что исходное структурно-фазовое состояние определяет формирование разного типа структур в зоне сплавления, зонах термического влияния и разный уровень микротвердости стали. В стали с меньшим содержанием углерода и исходной мелкозернистой, однородной феррито-бейнитной структурой при лазерной сварке сформирован сварной шов с лучшими механическими свойствами за счет получения в структуре феррита и гранулярного бейнита, чем в стали с более высоким содержанием углерода и феррито-перлитной крупнозернистой структурой.As a result of complex structural studies, it has been shown that the initial structural-phase state determines the formation of different types of structures in the fusion zone, heat-affected zones and different levels of steel microhardness. Steels with a lower carbon content and an initial fine-grained homogeneous ferrite-bainite structure during laser welding form a weld with better mechanical properties due to the production of ferrite and granular bainite in the structure than steels with a higher carbon content and a ferrite-pearlite coarse-grained structure

miR-155–5p predictive role to decelerate foam cell atherosclerosis through CD36, VAV3, and SOCS1 pathway

MicroRNAs (miRNAs) are noncoding RNA molecules that play a significant role in atherosclerosis pathogenesis through post-transcriptional regulation. In the present work, a bioinformatic analysis using TargetScan and miRdB databases was performed to identify the miRNAs targeting three genes involved in foam cell atherosclerosis (CD36, Vav3, and SOCS1). A total number of three hundred and sixty-seven miRNAs were recognized and only miR-155–5p was selected for further evaluation based on Venn analysis. Another objective of this study was to evaluate the biological process and regulatory network of miR-155–5p associated with foam cell atherosclerosis using DIANA, DAVID, Cytoscape, and STRING tools. Additionally, the comprehensive literature review was performed to prove the miR-155–5p function in foam cell atherosclerosis. miR-155–5p might be related with ox-LDL uptake and endocytosis in macrophage cell by targeting CD36 and Vav3 genes which was showed from the KEGG pathways hsa04979, hsa04666, hsa04145 H, hsa04810, and GO:0099632, GO:0060100, GO:0010743, GO:001745. Furthermore, miR-155–5p was also predicted to increase the cholesterol efflux from macrophage by inhibit SOCS1 expression based on KEGG pathway hsa04120. Eleven original studies were included in the review and strongly suggest the role of miR-155–5p in foam cell atherosclerosis inhibition

Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.British Heart Foundation Programme Grant (CS, PE); British Heart Foundation Project Grants PG/09/067/27901 (AB, VR), PG/13/55/30365 (LW, SF), PG/14/38/30862 (CR, VR), PG/16/44/32146 (JJ, EKT, SF); British Heart Foundation Studentship FS/14/8/30605 (BW, VR); MRC Fellowship MR/K023977/1 (RB); and European Union’s Horizon 2020 Marie Skłodowska-Curie Innovative Training Network, TRAIN 721532 (CN)

Role of microRNA-126 and -155 in atherosclerosis

Endotheliales miR-126 reguliert die Angiogenese und vaskuläre Integritäten sowie die Übertragung von miR-126 in endotheliale apoptotic bodies verringert die atherosklerotische Plaquebildung. Die Rolle von miR-126 in der endothelialen Zellregeneration ist unbekannt. Die endotheliale Denudation der A. carotis von miR-126-/-Apoe-/- und miR-126+/+Apoe-/-Mäusen ergab, dass die Deletion von miR-126 die Neointimabildung steigert und die Reparatur der Endothelzellen durch Hemmung ihrer Proliferation behindert. Eine Genomweite Array-Analyse zeigte, dass das in silico vorhergesagte miR-126-Zielgen, Dlk1, in verletzten Karotiden von miR-126-/-Apoe-/- Mäusen hochreguliert war. Strang-spezifisches Silencing von miR-126-3p/-5p in verletzten Arterien von Apoe-/- Mäusen zeigte, dass nur die Hemmung von miR-126-5p die Plaquebildung steigerte und die endotheliale Zellproliferation beeinträchtigte. Silencing von Dlk1 in verletzten Arterien von miR-126-/-Apoe-/- Mäusen verminderte die Neointimabildung und verbesserte die Endothelzellproliferation. Dies zeigt, dass miR-126-5p die Endothelzellproliferation nach Verletzung durch die Suppression von Dlk1 reguliert. Darüber hinaus verstärkte die Deletion von miR-126 die atherosklerotische Plaquebildung nach 3-monatiger Fütterung einer fettreichen Diät. Die Atherosklerose war jedoch nur in der thorakoabdominalen Aorta und nicht im Aortensinus von miR-126-/-Apoe-/- Mäusen erhöht. Die Expression von miR-126-5p, aber nicht die von miR-126-3p, war in der Aortenwurzel und an den Prädilektionsstellen für Atherosklerose von Apoe-/- Mäusen reduziert. Akute Verminderung des Blutflusses in der A. carotis durch eine partielle Ligation führte zu einer geringeren miR-126-5p und einer vermehrten Dlk1 Expression, dies zeigt, dass verminderter Blutfluss in Prädilektionsstellen die miR-126-5p/Dlk1 Expression reguliert. In humanen atherosklerotischen Läsionen korrelierte die miR-126-5p Expression negativ mit der endothelialen Dlk1 Expresssion und positiv mit der Endothelzellproliferation. Systemische Verabreichung von miR-126-5p reduzierte die Läsionsbildung und verbesserte die Endothelzellproliferation sowohl in miR-126-/-Apoe-/- als auch in miR-126+/+Apoe-/- Mäusen. Zusammenfassend sprechen die Ergebnisse dafür, dass miR-126-5p die Endothelzellregeneration nach Gefäßverletzung und während der Atherosklerose durch Suppression von Dlk1 fördert und vor einer Läsionsbildung schützt. Eine Anhebung des miR-126-5p Spiegels könnte daher eine mögliche Therapie gegen Atherosklerose sein. Makrophagen sind in der Bildung von atherosklerotischen Plaques involviert, da sie die Entzündungsreaktion verstärken. MiRs kontrollieren die Differenzierung und inflammatorische Aktivierung von Makrophagen durch die Regulierung wichtiger Signalwege, wie z. B. NF-kappaB. Allerdings ist die funktionelle Rolle von miRs in Makrophagen an der Entzündungsreaktion während der Atherogenese unbekannt. Das miR-Expressionsprofil in inflammatorischen Makrophagen, die mit LPS/IFNgamma stimuliert wurden und das in atherosklerotischen Läsionen der partiell ligierten A. carotis in Apoe-/- Mäusen wiesen beide eine gesteigerte Expression der miR-155 auf. Die miR-155 Expression war zudem auch in IFNgamma/moxLDL-stimulierten Makrophagen erhöht. Dies deutet darauf hin, dass die miR-155 eine Rolle in inflammatorischen Makrophagen spielt. Ein Leukozyten-spezifischer Mangel an miR-155 reduzierte die Plaquebildung in den partiell ligierten A. carotis von Apoe-/- Mäusen aufgrund einer verminderten Makrophagenakkumulation. In moxLDL/IFNgamma-stimulierten miR-155-/- Makrophagen war die Expression des Chemokins CCL2 vermindert verglichen mit miR-155+/+ Makrophagen. Da bekannt ist, dass CCL2 die Rekrutierung von Monozyten in atherosklerotischen Plaques fördert, könnte dadurch die geringere Makrophagenakkumulation in Plaques von Mäusen mit miR-155-/- Makrophagen erklärt werden. Entsprechend war die CCL2 Expression in miR-155-/- Makrophagen aus atherosklerotischen Plaques vermindert, was auf eine pro-inflammatorische Rolle der miR-155 während der Atherosklerose hinweist. Silencing von Bcl6, ein NF-kappaB-Inhibitor, in miR-155-/- Makrophagen führte zu einer gesteigerten CCL2 Expression nach Stimulation mit moxLDL/IFNgamma. Dies bedeutet, dass miR-155 durch Suppression von Bcl6 die CCL2 Expression in Makrophagen steigert. Die gesteigerte Expression von Bcl6 in miR-155-/- Makrophagen verminderte die atherogenen Inflammation und Plaquebildung. Entsprechend steigerte das Silencing von Bcl6 in der partiell ligierten A. carotis von Apoe-/- Mäusen mit miR-155-/- Makrophagen die Bildung von Plaques und CCL2. Dies bestätigt die funktionelle Rolle von Bcl6 in Entwicklung der Atherosklerose. Zusammengefasst zeigen diese Daten, dass miR-155 eine pro-inflammatorische Rolle in Makrophagen spielt und die Arteriosklerose durch Suppression der Bcl6 Expression fördert. Dies führt zu einer erhöhten CCL2 Expression und damit zu einer gesteigerten Makrophagenakkumulation