Hasil untuk "Organic chemistry"

Idalia Bilecka, M. Niederberger

P. Savage

P. Warneck

C. Hawker, K. Wooley

D. Hall

ThanhLoan Tran, Zhong-Yu Wang, Pei-Shan Li et al.

Coronary heart disease (CHD) is driven by endothelial dysfunction and chronic vascular inflammation. hsa-miR-2110 (miR-2110) has been associated with adverse cardiovascular outcomes, but its mechanistic role in CHD remains unclear. In this study, miR-2110 expression was quantified in peripheral blood from CHD patients and healthy controls. Functional effects were assessed in EA.hy926 endothelial cells following lentiviral overexpression of miR-2110. The target gene TRAF3 was identified by RNA sequencing, bioinformatic analysis, and validated by dual-luciferase reporter assays, RT-qPCR, and Western blotting. TRAF3 expression was further evaluated in CHD patient blood samples and in atherosclerotic lesions from ApoE−/− mice fed a high-fat diet. miR-2110 was significantly downregulated in CHD patients. Overexpression of miR-2110 in endothelial cells impaired proliferation and migration, induced S-phase arrest, reduced apoptosis, and promoted cellular senescence. TRAF3 was confirmed as a direct target of miR-2110. TRAF3 was significantly upregulated in CHD patients. In ApoE−/− mice, TRAF3 protein expression was increased in atherosclerotic lesions, predominantly within the tunica intima. Pathway enrichment predicted NF-κB–related signaling among the enriched pathways potentially associated with the miR-2110/TRAF3 axis. Together, our findings suggest that the miR-2110/TRAF3 axis represents a novel regulatory pathway involved in CHD, potentially relevant to endothelial dysfunction and inflammatory signaling.

Sarai Rojas-Jiménez, María Guadalupe Valladares-Cisneros, David Osvaldo Salinas-Sánchez et al.

<i>Euphorbia</i> is a large genus of the Euphorbiaceae family. Around 250 species of the <i>Euphorbia</i> genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different <i>Euphorbia</i> species have anti-cancer activity. In this review, we included compounds isolated from species of the <i>Euphorbia</i> genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords <i>Euphorbia</i> with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the <i>Euphorbia</i> genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%).

Barbara Rozbicka, Robert Koncki, Marta Fiedoruk-Pogrebniak

In this work, a microfluidic paper-based analytical device (µPAD) for simultaneous detection of Fe, Zn, and Mn ions using immobilized chromogenic reagents Ferene S, xylenol orange, and 1-(2-pyridylazo)-2-naphthol, respectively, is presented. As the effective recognition of analytes via respective chromogens takes place under extremely different pH conditions, experiments reported in this publication are focused on optimization of the µPAD architecture allowing for the elimination of potential cross effects. The paper-based microfluidic device was fabricated using low-cost and well-reproducible wax-printing technology. For optical detection of color changes, an ordinary office scanner and self-made RGB-data processing program were applied. Optimized and stable over time, µPADs allow fast, selective, and reproducible multianalyte determinations at submillimolar levels of respective heavy metal ions, which was confirmed by results of the analysis of solutions mimicking real samples of wastewater. The presented concept of simultaneous determination of different analytes that required extremely different conditions for detection can be useful for the development of other multianalyte microfluidic paper-based devices in the µPAD format.

Paola Mirra, Alessia Parascandolo, Graziella Marino et al.

Abstract The adipose tissue (AT) surrounding breast cancer (BC) plays a pivotal role in cancer progression and represents an optimal source for new biomarker discovery. The aim of this work was to investigate whether specific AT factors may have prognostic value in estrogen receptor-positive (ER+) BC. Proteoglycan Versican (VCAN), Insulin-like Growth Factor 1 (IGF1), Reticulon 4B (RTN4), chemokines CCL5 (also known as RANTES) and interleukin 8 (IL-8) are expressed in AT and may play important roles in BC progression. Peritumoral AT and tumoral biopsies were obtained from patients with ER+ BC (N = 23). AT specimens were collected also from healthy women (N = 17; CTRL-AT). The analysis of gene expression by qPCR revealed significantly higher mRNA levels of VCAN, IGF1, RTN4, and CCL5 in BC-AT compared to the CTRL-AT, and no difference in IL-8 mRNA levels. VCAN positively correlated with patient Body Mass Index (BMI) in BC-AT, while not in CTRL-AT. Moreover, VCAN and IGF1 positively correlated with RTN4 and negatively with CCL5. Interestingly, VCAN correlated with tumoral Ki67, while IGF1 with tumoral OCT4 that, in turn, correlated with tumoral Ki67 and patient BMI. Thus, peritumoral AT content of VCAN, and IGF1 are related to BC proliferation and aggressiveness.

Yuanbojiao Zuo, Chen Zhang, Yuan Zhou et al.

Abstract Background Gene editing has emerged as an exciting therapeutic development platform for numerous genetic and nongenetic diseases. Targeting lipid-modulating genes such as angiopoietin-related protein 3 (ANGPTL3) with gene editing offers hope for a permanent solution to lower cardiovascular disease risks associated with hypercholesterolemia. Results In this study, we developed a hepatocyte-specific base editing therapeutic approach delivered by dual adeno-associated virus (AAV) to enable hepatocyte-specific targeting of Angptl3 to lower blood lipid levels. Systemic AAV9-mediated delivery of AncBE4max, a cytosine base editor (CBE), targeting mouse Angptl3 resulted in the installation of a premature stop codon in Angptl3 with an average efficiency of 63.3 ± 2.3% in the bulk liver tissue. A near-complete knockout of the ANGPTL3 protein in the circulation were observed within 2–4 weeks following AAV administration. Furthermore, the serum levels of triglyceride (TG) and total cholesterol (TC) were decreased by approximately 58% and 61%, respectively, at 4 weeks after treatment. Conclusions These results highlight the promise of liver-targeted Angptl3 base editing for blood lipid control.

A. Cholakian, A. Cholakian, A. Cholakian et al.

<p>Organic aerosol (OA) still remains one of the most difficult components of the atmospheric aerosols to simulate, given the multitude of its precursors, the uncertainty in its formation pathways, and the lack of measurements of its detailed composition. The LANDEX (LANDes Experiment) project, during its intensive field campaign in summer 2017, gives us the opportunity to compare biogenic secondary OA (BSOA) and its precursors and oxidants obtained within and above the Landes forest canopy to simulations performed with CHIMERE, a state-of-the-art regional chemistry transport model. The Landes forest is situated in the southwestern part of France and is one of the largest anthropized forests in Europe (<span class="inline-formula">1×10⁶</span> ha). The majority of the forest is comprised of maritime pine trees, which are strong terpenoid emitters, providing a large potential for BSOA formation. In order to simulate OA buildup in this area, a specific model configuration setup adapted to the local peculiarities was necessary. As the forest is nonhomogeneous, with interstitial agricultural fields, high-resolution 1 km simulations over the forest area were performed. Biogenic volatile organic compound (BVOC) emissions were predicted by MEGAN, but specific land cover information needed to be used and was thus chosen from the comparison of several high-resolution land cover databases. Moreover, the tree species distribution needed to be updated for the specific conditions of the Landes forest. In order to understand the canopy effect in the forest, canopy effects on vertical diffusivity, winds, and radiation were implemented in the model in a simplified way. The refined simulations show a redistribution of BVOCs with a decrease in isoprene and an increase in terpenoid emissions with respect to the standard case, both of which are in line with observations. Corresponding changes to simulated BSOA sources are tracked. Very low nighttime ozone, sometimes near zero, remains overestimated in all simulations. This has implications for the nighttime oxidant budget, including <span class="inline-formula">NO₃</span>. Despite careful treatment of physical conditions, simulated BSOA is overestimated in the most refined simulation. Simulations are also compared to air quality sites surrounding the Landes forest, reporting a more realistic simulation in these stations in the most refined test case. Finally, the importance of the sea breeze system, which also impacts species concentrations inside the forest, is made evident.</p>

Hanwen Ren, Xiansu Liu, Shanshan Wei et al.

The progression of Alzheimer’s disease (AD) is positively correlated with the phosphorylation damage of Tau-441 protein, which is the marker with the most potential for the early detection of AD. The low content of Tau-441 in human serum is a major difficulty for the realization of content detection. Herein, we prepared an electrochemical immunosensor modified with Poly(3,4-ethylene-dioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS)/Carboxylated multi-walled carbon nanotube (MWCNTs-COOH) nanocomposites based on electrochemical immunoassay technology for the low-concentration detection of Tau-441. The immunosensor based on the nanocomposite can take advantage of the characteristics of conductive polymers to achieve electrical signal amplification and use MWCNTs-COOH to increase the contact area of the active site and bond with the Tau-441 antibodies on the electrode. The physicochemical and electrical properties of PEDOT: PSS/MWCNTs-COOH were studied by in situ characterization techniques and electrochemical characterization methods, indicating that the immunosensor has high selectivity and sensitivity to the Tau-441 immune reaction. Under optimized optimal conditions, the electrochemical immunosensor detected a range of concentrations of Tau-441 to obtain a low detection of limit (0.0074 ng mL⁻¹) and demonstrated good detection performance through actual human serum sample testing experiments. Therefore, the study provides an effective reference value for the early diagnosis of AD.

Ivan Aftanaziv, Myroslav Malovanyy, Lilija Shevchuk et al.

The results of an experimental study of efficiency of the cavitation treatment of a fuel mixture, based on A-95 gasoline and distilled water, for automobile internal combustion engines are presented. Cavitation treatment of this fuel mixture at a percentage of water/gasoline of 17/83 % allows increasing the cost of gasoline up to 15-20 % when operating engines on flat and sloping sections of roads and in traffic jams. Due to the cavitation treatment, the engine power is reduced by only 6/7 %. The design of the created automobile electromagnetic vibrating cavitator is described. Its application will not only save fuel, but increase the completeness of combustion of water-gasoline fuel mixture, i.e. improve the environment, as well %.

Yonghai Li, Haiyao Gao, Tobias M. Brunner et al.

Abstract Background Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE). Methods We assessed the therapeutic effect of MB-MSCs transplanted via either intravenous (i.v.) or intraperitoneal (i.p.) route in EAE in comparison with umbilical cord-derived MSCs (UC-MSCs). We used histology to assess myelin sheath integrity and infiltrated immune cells in CNS and flow cytometry to evaluate EAE-associated inflammatory T cells and antigen-presenting cells in lymphoid organs. Results We observed disease-ameliorating effects of MB-MSCs when transplanted at various stages of EAE (day − 1, 6, 10, and 19), via either i.v. or i.p. route, with a potency comparable to UC-MSCs. We observed reduced Th1 and Th17 cell responses in mice that had received MB-MSCs via either i.v. or i.p. injection. The repressed Th1 and Th17 cell responses were associated with a reduced frequency of plasmacytoid dendritic cells (pDCs) and a suppressed co-stimulatory capacity of pDCs, cDCs, and B cells. Conclusions Our data demonstrate that the readily available MB-MSCs significantly reduced the disease severity of EAE upon transplantation. Thus, they have the potential to be developed as ready-to-use allo-MSCs in MS-related inflammation. Graphical abstract

László KISS, Sándor KUNSÁGI-MÁTÉ

This study reveals the behavior of resorcinol, phloroglucinol and pyrogallol in several non-aqueous solvents (acetonitrile, acetone, dimethyl sulphoxide, dimethyl formamide, nitrobenzene, nitromethane, dichloromethane, methanol). The voltammetric curves showed that the results obtained with the outlined compounds depend strongly on the solvent used. Resorcinol and phloroglucinol undergo some fouling during their electrooxidation while pyrogallol gave reproducible voltammograms in many solvents. The optimal solvent was chosen then for the determination of pyrogallol in cooking oil taking into consideration the antifouling, miscibility, permittivity and viscosity effects with steady-state voltammetry by using microelectrode.

Carlotta Peticone, David De Silva Thompson, Nikolay Dimov et al.

Using microspherical scaffolds as building blocks to repair bone defects of specific size and shape has been proposed as a tissue engineering strategy. Here, phosphate glass (PG) microcarriers doped with 5 mol % TiO 2 and either 0 mol % CoO (CoO 0%) or 2 mol % CoO (CoO 2%) were investigated for their ability to support osteogenic and vascular responses of human mesenchymal stem cells (hMSCs). Together with standard culture techniques, cell-material interactions were studied using a novel perfusion microfluidic bioreactor that enabled cell culture on microspheres, along with automated processing and screening of culture variables. While titanium doping was found to support hMSCs expansion and differentiation, as well as endothelial cell-derived vessel formation, additional doping with cobalt did not improve the functionality of the microspheres. Furthermore, the microfluidic bioreactor enabled screening of culture parameters for cell culture on microspheres that could be potentially translated to a scaled-up system for tissue-engineered bone manufacturing.

Adriana Nowak, Małgorzata Zakłos-Szyda, Dorota Żyżelewicz et al.

Acrylamide (AA) toxicity remains an interesting subject in toxicological research. The aim of the research performed in this paper was to determine mechanisms of cyto- and genotoxic effects of AA on the human colon adenocarcinoma cell line Caco-2, to estimate the inhibitory concentration (IC)₅₀ values in cell viability assays, to measure the basal and oxidative DNA damage as well as the oxidative stress leading to apoptosis, and to assess the morphological changes in cells using microscopic methods. It has been proven that AA induces cytotoxic and genotoxic effects on Caco-2 cells. Higher cytotoxic activity was gained in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay compared with the PrestoBlue assay, with IC₅₀ values of 5.9 and 8.9 mM after 24 h exposure, respectively. In the single-cell gel electrophoresis assay, the greatest DNA damage was caused by the highest concentration of acrylamide equal to 12.5 mM (89.1% &#177; 0.9%). AA also induced oxidative DNA damage and generated reactive oxygen species (ROS), which was concentration dependent and correlated with the depletion of mitochondrial membrane potential and apoptosis induction. In the microscopic staining of cells, AA in the dosage close to the IC₅₀ induced morphological changes typical for apoptosis. Taken together, these results demonstrate that AA has a pro-oxidative effect on Caco-2 cells, leading to apoptotic cell death.

Ildikó Línzembold, Dalma Czett, Katalin Böddi et al.

Flavonoids and carotenoids possess beneficial physiological effects, such as high antioxidant capacity, anticarcinogenic, immunomodulatory, and anti-inflammatory properties, as well as protective effects against UV light. The covalent coupling of hydrophobic carotenoids with hydrophilic flavonoids, such as daidzein and chrysin, was achieved, resulting in new amphipathic structures. 7-Azidohexyl ethers of daidzein and chrysin were prepared in five steps, and their azide-alkyne [4 + 2] cycloaddition with pentynoates of 8&#8242;-apo-&#946;-carotenol, zeaxanthin, and capsanthin afforded carotenoid&#8722;flavonoid conjugates. The trolox-equivalent antioxidant capacity against ABTS^&#8226;+ radical cation and self-assembly of the final products were examined. The 1:1 flavonoid&#8722;carotenoid hybrids generally showed higher antioxidant activity than their parent flavonoids but lower than that of the corresponding carotenoids. The diflavonoid hybrids of zeaxanthin and capsanthin, however, were found to exhibit a synergistic enhancement in antioxidant capacities. ECD (electronic circular dichroism) and UV-vis analysis of zeaxanthin&#8722;flavonoid conjugates revealed that they form different optically active J-aggregates in acetone/water and tetrahydrofuran/water mixtures depending on the solvent ratio and type of the applied aprotic polar solvent, while the capsanthin derivatives showed no self-assembly. The zeaxanthin bis-triazole conjugates with daidzein and with chrysin, differing only in the position of a phenolic hydroxyl group, showed significantly different aggregation profile upon the addition of water.

A. Covington, T. Dickinson

C. Cherrington, M. Hinton, G. Mead et al.