AimsMedical treatment of arterial thrombosis is mainly directed against platelets and coagulation factors, and can lead to bleeding complications. Novel antithrombotic therapies targeting immune cells and neutrophil extracellular traps (NETs) are currently being investigated in animals. We addressed whether immune cell composition of arterial thrombi induced in mouse models of thrombosis resemble those of human patients with acute myocardial infarction (AMI).Methods and resultsIn a prospective cohort study of patients suffering from AMI, 81 human arterial thrombi were harvested during percutaneous coronary intervention and subjected to detailed histological analysis. In mice, arterial thrombi were induced using two distinct experimental models, ferric chloride (FeCl3) and wire injury of the carotid artery. We found that murine arterial thrombi induced by FeCl3 were highly concordant with human coronary thrombi regarding their immune cell composition, with neutrophils being the most abundant cell type, as well as the presence of NETs and coagulation factors. Pharmacological treatment of mice with the protein arginine deiminase (PAD)-inhibitor Cl-amidine abrogated NET formation, reduced arterial thrombosis and limited injury in a model of myocardial infarction.ConclusionsNeutrophils are a hallmark of arterial thrombi in patients suffering from acute myocardial infarction and in mouse models of arterial thrombosis. Inhibition of PAD could represent an interesting strategy for the treatment of arterial thrombosis to reduce neutrophil-associated tissue damage and improve functional outcome.

Abamectin, a blend of the natural avermectins B and B, is a widely-used insecticide/miticide with relatively low toxicity to mammals. Exposure to high doses of it, however, leads to cholinergic-like neurotoxic effects. Butyrylcholinesterase, which is best known for its abundant presence in plasma, is a serine hydrolase loosely coupled with the cholinergic system. It protects and supports the neurotransmitter function of its sister enzyme acetylcholinesterase. Here, using experimental and computational studies, we provide evidence demonstrating that abamectin is a potent (IC = 10.6 μM; K = 2.26 ± 0.35 μM) inhibitor of horse serum butyrylcholinesterase and that it interacts with the enzyme in a reversible, competitive manner predictively to block the mouth of the active-site gorge of the enzyme and to bind to several critical residues that normally bind/hydrolyze choline esters.

Background Hormone production by the thyroid gland is a prime aspect of maintaining body homeostasis. In this study, the ability of single artificial intelligence (AI)-based models, namely multi-layer perceptron (MLP), support vector machine (SVM), and Hammerstein–Weiner (HW) models, were used in the simulation of thyroidism status. The study's primary aim is to unveil the best performing model for the simulation of thyroidism status using hepatic enzymes and hormones as the independent variables. Three statistical metrics were used in evaluating the performance of the models, namely determination coefficient (R2), correlation coefficient (R), and mean squared error (MSE). Results Considering the quantitative and visual presentation of the results obtained, it has been observed that the MLP model showed higher performance skills than SVM and HW, which improved their performances up to 3.77% and 12.54%, respectively, in the testing stages. Furthermore, to boost the performance of the single AI-based models, three different ensemble approaches were employed, including neural network ensemble (NNE), weighted average ensemble (WAE), and simple average ensemble (SAE). The quantitative predictive performance of the NNE technique boosts the performance of SAE and WAE approaches up to 2.85% and 1.22%, respectively, in the testing stage. Conclusions Comparative performance of the ensemble techniques over the single models showed that NNE outperformed all the three AI-based models (MLP, SVM, and HW) and boosted their performance accuracy up to 7.44%, 11.212%, and 19.98%, respectively, in the testing stages.

Avermectins are a group of macrocyclic lactones that are commonly used as pesticides to treat pests and parasitic worms. Some members of the avermectin family, such as ivermectin, have been found to exhibit anti-proliferative activity toward cancer cells. This study aimed to investigate the potential anti-cancer activities of avermectin B1a using the HCT-116 colon cancer cell line. The MTT assay was used to calculate the IC50 by incubating cells with increasing doses of avermectin B1a for 24, 48, and 72 h. Flow cytometry was used to evaluate apoptosis following the 24 h incubation of cells. The migration capacity of the HCT-116 cells in the absence or presence of avermectin B1a was also investigated. Finally, tubulin polymerization in the presence of avermectin B1a was evaluated. Avermectin B1a presented anti-proliferative activity with an IC50 value of 30 μM. Avermectin B1a was found to promote tubulin polymerization at 30 μM. In addition, avermectin B1a induced apoptosis in HCT-116 cells and substantially diminished their ability to migrate. Avermectin B1a exhibits significant anti-cancer activity and enhances tubulin polymerization, suggesting that it can be used as a promising microtubule-targeting agent for the development of future anticancer drugs.

The article was originally published with incorrect wording in the third paragraph of the Results section. The sentence originally appeared as "When the kinetics of BChE inhibition was graphed in the Lineweaver-Burk plot of 1/ specific activity versus 1/[abamectin], the results exhibited the unique characteristics of competitive inhibition (Fig. 2A)" It has been corrected to: "When the kinetics of BChE inhibition was graphed in the Lineweaver-Burk plot of 1/specific activity versus 1/[BTCh], the results exhibited the unique characteristics of competitive inhibition (Fig. 2A)."