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101.
Eva Havrnkov Vladimír Garaj rka Mascaretti Andrea Angeli Zuzana Soldnov Miroslav Kemka Jozef Moty
ka Marie Brzdov Jozef Csllei Josef Jampílek Claudiu T. Supuran 《International journal of molecular sciences》2022,23(1)
A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with KIs = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity. 相似文献
102.
Eva Harlacher Julia Wollenhaupt Constance C. F. M. J. Baaten Heidi Noels 《International journal of molecular sciences》2022,23(1)
Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD. 相似文献
103.
Gabriela Loscalzo Julia Scheel Jos Santiago Ibaez-Cabellos Eva García-Lopez Shailendra Gupta Jos Luis García-Gimenez Salvador Mena-Moll Alfredo Perales-Marín Jos Morales-Rosell 《International journal of molecular sciences》2022,23(1)
In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease. 相似文献
104.
This paper is concerned with the design of reconfigurable control laws for fault-tolerant systems. From the control design point of view the issue of performance robustness during the system normal operation versus failure sensitivity at the time of a system component failure is addressed. To achieve a balanced design, a parametrized set of controllers satisfying a prescribed performance level is first constructed, and then the parameter is optimized under a detection criterion that sensitizes the measurements to some specific failures. An example involving aircraft surface impairment is given to explain the procedure for obtaining the optimized design. 相似文献
105.
The influence of extraction of reinforced fibres on surface properties and the curing reaction of epoxy resin matrix in composites were investigated. With increasing fibre surface polarity, as the result of the extraction, the resin wettability was improved and the reaction rate of curing of the epoxy resin matrix increased. The wettability and the reaction rate oppositely decreased with decreasing fibre surface polarity. 相似文献
106.
Nina Kunov Henrieta Havalov Gabriela Ondrovi
ov Barbora Stojkovi
ov Jacob A. Bauer Vladena Bauerov-Hlinkov Vladimir Pevala Eva Kutejov 《International journal of molecular sciences》2022,23(3)
Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans. In this review, we focus on characterizing the structure, function, and substrate specificities of mitochondrial processing peptidases, as well as the connection of their malfunctions to severe human diseases. 相似文献
107.
Ramiro Vilchez-Vargas Franz Salm Eva B. Znalesniak Katharina Haupenthal Denny Schanze Martin Zenker Alexander Link Werner Hoffmann 《International journal of molecular sciences》2022,23(3)
Here, the spatial distribution of the bacterial flora along the murine alimentary tract was evaluated using high throughput sequencing in wild-type and Tff3-deficient (Tff3KO) animals. Loss of Tff3 was linked to increased dextran sodium sulfate-induced colitis. This systematic study shows the results of 13 different regions from the esophagus to the rectum. The number of bacterial species (richness) increased from the esophagus to the rectum, from 50 to 200, respectively. Additionally, the bacterial community structure changed continuously; the highest changes were between the upper/middle and lower gastrointestinal compartments when comparing adjacent regions. Lactobacillus was the major colonizer in the upper/middle gastrointestinal tract, especially in the esophagus and stomach. From the caecum, a drastic diminution of Lactobacillus occurred, while members of Lachnospiraceae significantly increased. A significant change occurred in the bacterial community between the ascending and the transverse colon with Bacteroidetes being the major colonizers with relative constant abundance until the rectum. Interestingly, wild-type and Tff3KO animals did not show significant differences in their bacterial communities, suggesting that Tff3 is not involved in alterations of intraluminal or adhesive microbiota but is obviously important for mucosal protection, e.g., of the sensitive stem cells in the colonic crypts probably by a mucus plume. 相似文献
108.
Eva Lidén Michael Persson Elis Carlström Roger Carlsson 《Journal of the American Ceramic Society》1991,74(6):1335-1339
Pressureless sintering of silicon nitride requires addition of sintering agents. The main part of this study was done in order to homogenize the distribution of sintering agents, in this case Y2 O3 , in a silicon nitride matrix. Colloidal 10-nm Y2 O3 Particles were electrostatically adsorbed on Si3 N4 particle surfaces. The adsorption was studied by X-ray fluorescence analysis and electrophoretic measurements. Addition of Y2 O3 sol to a Si3 N4 suspension decreased the viscosity of the suspension. The slip casting properties of Si3 N4 suspensions with added Y2 O3 sol were examined, and the homogeneity of Y2 O3 in the green compacts was compared with conventionally prepared samples. An improved microstructural homogeneity was obtained when Y2 O3 sol particles were adsorbed on the Si3 N4 particle surfaces. 相似文献
109.
110.
Eva Klimánková Kateřina Holadová Jana Hajšlová Tomáš Čajka Jan Poustka Martin Koudela 《Food chemistry》2008
A headspace solid-phase microextraction (HS-SPME) method coupled to gas chromatography–ion trap mass spectrometry (GC–ITMS) has been developed and applied for profiling of volatile compounds released from five Ocimum basilicum L. cultivars grown under both organic and conventional conditions. Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC–TOFMS) was employed for confirmation of identity of volatiles extracted from the basil headspace by SPME. 相似文献