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Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer's disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50 = 97 ± 0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p less then 0.05). Improved pharmacokinetic parameters, viz., Log P o/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD.Inflammatory diseases are a real public health problem worldwide. Many synthetic drugs used in the treatment of inflammatory diseases such as steroidal anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressive drugs have harmful side effects. However, there are natural products like propolis, which is traditionally used in the treatment of pain. The objective of this work was to evaluate the anti-inflammatory and analgesic activities of the ethyl ester of arachic acid, a compound isolated from Cameroonian propolis. The ethyl ester of arachic acid was isolated by chromatography of the ethanolic extract of propolis harvested at Tala-Mokolo (Far North Region of Cameroon) and identified by nuclear magnetic resonance (NMR) spectra and the 1H-1H correlated spectroscopy. The anti-inflammatory and analgesic properties of oral administration of arachic acid ethyl ester (12.5, 25.0, and 50.0 mg/kg bw) were evaluated using carrageenan-induced paw edema, xylene-induced ear edema, cotton pellets-induced granuloma formation, and hot plate test in rat. Arachic acid ethyl ester produced maximum inhibition at 50.0 mg/kg for carrageenan-induced paw edema (62.5%), xylene-induced ear edema (54.5%), cotton pellet-induced granuloma (47.4%), and increased mean latency for hot plate test in rats. These results show clearly that the arachic acid ethyl ester has acute and chronic anti-inflammatory properties as well as central analgesic properties. This justifies the use of propolis in the treatment of pain in traditional medicine.[This corrects the article DOI 10.1155/2018/9812041.].Mangroves are a group of plant species that occupy the coastal intertidal zone and are major components of this ecologically important ecosystem. Mangroves belong to about twenty diverse families. Here, we sequenced and assembled chloroplast genomes of 14 mangrove species from eight families spanning five rosid orders and one asterid order Fabales (Pongamia pinnata), Lamiales (Avicennia marina), Malpighiales (Excoecaria agallocha, Bruguiera sexangula, Kandelia obovata, Rhizophora stylosa, and Ceriops tagal), Malvales (Hibiscus tiliaceus, Heritiera littoralis, and Thespesia populnea), Myrtales (Laguncularia racemosa, Sonneratia ovata, and Pemphis acidula), and Sapindales (Xylocarpus moluccensis). These chloroplast genomes range from 149 kb to 168 kb in length. A conserved structure of two inverted repeats (IRa and IRb, ~25.8 kb), one large single-copy region (LSC, ~89.0 kb), and one short single-copy region (SSC, ~18.9 kb) as well as ~130 genes (85 protein-coding, 37 tRNAs, and 8 rRNAs) was observed. We found the lowest divergence in the IR regions among the four regions. We also identified simple sequence repeats (SSRs), which were found to be variable in numbers. Most chloroplast genes are highly conserved, with only four genes under positive selection or relaxed pressure. Combined with publicly available chloroplast genomes, we carried out phylogenetic analysis and confirmed the previously reported phylogeny within rosids, including the positioning of obscure families in Malpighiales. Our study reports 14 mangrove chloroplast genomes and illustrates their genome features and evolution.ATPase family AAA domain-containing protein 2 (ATAD2), a chromatin regulator and an oncogenic transcription cofactor, is frequently overexpressed in many cancers, particularly in hepatocellular carcinoma (HCC). By integrating open-access online mRNA datasets and our institutional tissue data on HCC, the clinical role and functions of ATAD2 were analyzed by bioinformatic algorithms. We systematically examined ATAD2 expression in HCC based on a large sample population, integrating data from our institution and the GEO, Oncomine, and TCGA datasets. Aberrant ATAD2 expression related to pathways was identified by bioinformatic algorithms. The effects of ATAD2 downregulation on the cycle cell were also determined. A pooled analysis from 28 datasets indicated that ATAD2 overexpression was found in HCC (SMD = 8.88, 95% CI 5.96-11.81, P less then 0.001) and was correlated with poor survival. selleck screening library Subgroup analysis of Asian patients with a serum alpha-fetoprotein (AFP) concentration less then 200 ng/ml in stage I + II selopment of therapeutic treatments for cancer.Materials and methods The petroleum ether (petrol), dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butyl alcohol (n-BuOH) fractions were isolated from alcohol extracts of D. moldavica L. Total phenolic and flavonoid contents and in vitro antioxidant activities of different fractions were evaluated. H9c2 cells were then treated with D. moldavica L. extracts before challenging with H2O2. Cell viability was determined by colorimetric assay, and ELISA was used to measure the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). Apoptosis levels and mitochondrial membrane potential were measured by flow cytometry. The expressions of cell apoptosis regulatory proteins caspase-3, Bax, and Bcl-2 were determined by western blotting. Results Our results demonstrated that the EtOAc fraction from D. moldavica L. ethanol extract, which is rich in phenolic and flavonoid active constituents, had the strongest free radical scavenging activity. Additionally, this fraction increased H2O2-induced reduction in cell viability, SOD activity, and mitochondrial membrane potential.
Homepage: https://www.selleckchem.com/
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