Myeloperoxidase (MPO) is an attractive therapeutic target against inflammation. Herein, we developed an inhibitor-like rule, based on known MPO inhibitors, and generated a target database containing 6546 molecules with privileged inhibitory properties. Using a structure-based approach validated by decoys, robust statistical metrics, redocking, and cross-docking, we selected 10 putative MPO inhibitors with high chemical diversity. At 20 μM, six of these 10 compounds (i.e., 60% success rate) inhibited more than 20% of the chlorinating activity of the enzyme. Additionally, we found that compound ZINC9089086 forms hydrogen bonds with Arg233 and with the hemic carboxylate. It makes a π-stacking interaction with the heme group and displays a high affinity for the enzyme active site. When incubated with purified MPO, ZINC9089086 inhibited the chlorinating activity of the enzyme with an IC50 of 2.2 ± 0.1 μM in a reversible manner. Subsequent experiments revealed that ZINC9089086 inhibited hypochlorous acid production in dHL-60 cells and human neutrophils. Furthermore, the theoretical ADME/Tox profile indicated that this compound exhibits low toxicity risks and adequate pharmacokinetic parameters, thus making ZINC9089086 a very promising candidate for preclinical anti-inflammatory studies. Overall, our study shows that integrating an inhibitor-like rule with a validated structure-based methodology is an excellent approach for improving the success rate and molecular diversity of novel MPO inhibitors with good pharmacokinetics and toxicological profiles. By combining these tools, it was possible to increase the assurance rate, which ultimately diminishes the costs and time needed for the acquisition, synthesis, and evaluation of new compounds.Lythrum salicaria herb (LSH) was applied in diarrhea therapy since ancient times. Despite empirically referenced therapeutic effects, the bioactivity mechanisms and chemical constituents responsible for pharmacological activity remain not fully resolved. Taking into consideration the historical use of LSH in treatment of diarrhea in humans and farm animals, the aim of the study was to examine in vitro the influence of LSH and its C-glycosylic ellagitannins on processes associated with maintaining intestinal epithelium integrity and enteropathogenic Escherichia coli (EPEC) growth and adhesion. LSH was not only inhibiting EPEC growth in a concentration dependent manner but also its adhesion to IPEC-J2 intestinal epithelial cell monolayers. Inhibitory activity toward EPEC growth was additionally confirmed ex vivo in distal colon samples of postweaning piglets. LSH and its dominating C-glycosylic ellagitannins, castalagin (1), vescalagin (2), and salicarinins A (3) and B (4) were stimulating IPEC-J2 monolayer formation by enhancing claudin 4 production. Parallelly tested gut microbiota metabolites of LSH ellagitannins, urolithin C (5), urolithin A (6), and its glucuronides (7) were inactive. The activities of LSH and the isolated ellagitannins support its purported antidiarrheal properties and indicate potential mechanisms responsible for its beneficial influence on the intestinal epithelium.Consumption of seafood is a common route of cadmium ion (Cd2+) exposure to consumers. The seafood matrices may alter the toxicity profile of Cd2+ due to the interaction between Cd2+ and biomacromolecules in seafood. In this study, enhanced cytotoxicity of Cd2+ was found in the presence of an abalone gonad sulfated polysaccharide (AGSP) and the mechanism was investigated at a metabolic level.  https://www.selleckchem.com/products/s64315-mik665.html  The formation of the AGSP-Cd2+ complex was demonstrated by isothermal titration calorimetry. The level of reactive oxygen species (ROS) increased and mitochondrial membrane potential reduced upon exposure to the AGSP-Cd2+ complex as compared with those of Cd2+ exposure. The decreased cell viability after incubation with the AGSP-Cd2+ complex also suggested enhanced Cd2+ toxicity induced by AGSP. The metabolomics and lipidomics analysis revealed that, compared with the Cd2+ group, the AGSP-Cd2+ downregulated the phospholipid metabolism and resulted in more serious damage in the cellular membrane. The lipid metabolism disorder, in turn, amplified the generation of ROS, leading to a decrease in cell viability. These results provided new evidence of the enhanced Cd2+ toxicity upon interaction with seafood polysaccharides, and much attention should be paid to the effect of food ingredients on heavy metal ion toxicity.Cerebral ischemia/reperfusion (I/R)-induced injury is a common phenomenon of stroke, and the effective treatment for I/R-induced brain tissue damage is limited. Breviscapine has been widely used in China as herbal medicine to treat cardiovascular diseases for hundreds of years and has been demonstrated to possess potent cardiovascular pharmacological effects. This study aims to investigate the neuroprotective effect of breviscapine on cerebral I/R-induced injury. The rat model of middle cerebral artery occlusion (MCAO) was applied in our study. The cerebral I/R rats received multiple injections of breviscapine. All rats were subject to neurological behavior tests by open field test and Morris water maze test. The pro-inflammatory cytokines and oxidative stress marker levels were determined by ELISA and colorimetric analysis, respectively. We demonstrated that administration of breviscapine dose-dependently ameliorated cerebral I/R-induced injury and improved the neurological performance of cerebral I/R rats. Further studies illustrated that breviscapine treatment effectively attenuated inflammatory cytokine expression, reduced oxidative stress, and pro-apoptosis protein expression and inhibited the activation of NF-κB signaling and microglia in the I/R injury tissues. Breviscapine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medicine for the treatment of cerebral I/R-induced injury.Lattice strain in oxygen ion conductors can be used to tune their functional properties for applications in fuel cells, sensors, or catalysis. However, experimental measurements of thin film strain in both in- and out-of-plane directions can be experimentally challenging. We propose a method for measuring strain in rare-earth doped ceria thin films by polarized Raman spectroscopy. We study epitaxial CeO2 films substituted by La, Gd, and Yb grown on MgO substrates with BaZrO3 and SrTiO3 interlayers, where different levels of strain are generated by annealing at distinct temperatures. The films show in-plane compression and out-of-plane expansion, resulting in a lowering from the bulk cubic to tetragonal lattice symmetry. This leads to the splitting of the F2g Raman mode in the cubic phase to B2g and E g modes in the tetragonal lattice. The symmetry and frequency of these modes are determined by polarized Raman in the backscattering and right-angle scattering geometries as well as by first-principal calculations.