A statistical learning framework for predicting left ventricular ejection fraction based on glutathione peroxidase-3 level in ischemic heart disease.

Ischemic heart disease (IHD) is the most prevalent cardiovascular disease. The left ventricular ejection fraction (LVEF) is a well-validated index of the systolic function of the left ventricle and it gradually decreases in IHD. We aimed to develop a new strategy for examining the relationship between serum glutathione peroxidase 3 (GPx3; a possible antioxidant protector against IHD) and the LVEF of IHD patients. To overcome the problem of small, imbalanced, and multicollinear datasets, we adopted leave-one-out cross-validation to maximize the size of the training set, the Youden index to reflect the biased distribution of events, and regularization or dimension transform techniques to reduce the effect of multicollinearity. For the outcome variable of LVEF, five classification methods were tested for six previously selected features with and without GPx3. High GPx3 levels (≥5.314 µg/mL) were closely related to a reduced LVEF (<50%). The presented statistical learning framework is effective for small and imbalanced data with multicollinearity such as clinical data.

MiR-921 directly downregulates GPx3 in A549 lung cancer cells.

Glutathione peroxidase 3 (GPx3), a major antioxidant enzyme in plasma, catalyzes the reduction of H2O2, lipid peroxides and organic hydroperoxides by reducing glutathione (GSH). Hypermethylation of the GPx3 promoter and suppression of GPx3 expression are associated with inflammation, tumorigenesis, and response to chemotherapy in various types of cancer. We previously reported the possibility of GPx3 as a serological marker for lung cancer. In this study, we assessed the role of the microRNA (miRNA) hsa-miR-921 (miR-921) in the regulation of GPx3 expression in A549 lung cancer cells. The expression patterns of the miRNAs of A549, H1650, and H1975 cells were compared and analyzed. Of 25 miRNAs from the A549 cell line, the expression of 10 decreased and the expression of 15 increased in comparison to the miRNAs from the other cell lines. Of the miRNAs with reduced expression, the most reduced miRNA was miR-921 and the expected binding site of which is in the 3'-untranslated region (UTR) of GPx3. We found that miR-921 inhibited the expression of GPx3 and bound directly to the 3'-UTR of GPx3.

Caffeoylserotonin suppresses THP-1 monocyte adhesion and migration via inhibition of the integrin ß1/FAK/Akt signalling pathway.

We investigated the effect of caffeoylserotonin (CaS) on THP-1 monocyte migration and adhesion to fibronectin in response to MCP-1. CaS decreased monocyte adhesion and migration induced by MCP-1, together with CCR2 expression and α5ß1 integrin, and activated ß1 integrin expression on the cell surface. CaS also inhibited FAK and Akt phosphorylation. We found that CaS had anti-inflammatory activity based on inhibition of adhesion and migration via inhibition of the integrin ß1/FAK/Akt signalling pathway. Thus, the inhibitory effects of CaS on monocyte function may support the future development of this compound as a potential treatment for inflammation-dependent diseases.

Cytoprotective activities of hydroxycinnamic acid amides of serotonin against oxidative stress-induced damage in HepG2 and HaCaT cells.

Hydroxycinnamic acid amides of serotonin (HCAAS) [caffeoylserotonin (compound 1), p-coumaroylserotonin (compound 2), and feruloylserotonin (compound 3)] are secondary metabolites produced in plants. The aim of this study was to investigate the cytoprotective effects of HCAAS based on intracellular reactive oxygen radical (ROS) generation, lipid peroxidation, protein carbonylation, and phosphorylation of histone H2AX in H(2)O(2) treated-HepG2 and HaCaT cells. We have shown that HCAAS showed various strong antioxidant activities in hydrogen peroxide treated both cell lines, suggesting that these compounds may play as chemotherapeutic agents for preventing or reducing the oxidative stress-induced diseases.

HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables.

Biogenic monoamines such as serotonin, tryptamine, and tyramine function as neurotransmitters and mitogenic factors in animals and are involved in flowering, morphogenesis, and protection from and adaptation to environmental changes in plants. In plants, serotonin and tyramine are conjugated to form phenolic compounds via thioester linkages during the synthesis of hydroxycinnamic acid amides, including p-coumaroylserotonin (CS), feruloylserotonin (FS), p-coumaroyltyramine (CT), and feruloyltyramine (FT). In this study, we determined the amounts of the biogenic monoamines CS, FS, CT, and FT in commonly consumed vegetables using high-performance liquid chromatography. Serotonin, tryptamine, and tyramine were detected in all vegetables tested. The serotonin levels ranged from 1.8 to 294 microg/g of dry weight, the tryptamine levels ranged from 0.8 to 372 microg/g of dry weight, and the tyramine levels ranged from 1.4 to 286 microg/g of dry weight. The highest serotonin and tryptamine contents were found in tomato and cherry tomato (140.3-222 microg/g of dry weight), while paprika and green pepper had higher tyramine contents than the other vegetables (286 and 141.5 microg/g of dry weight, respectively). Overall, the levels of CS, FS, CT, and FT ranged from 0.03 to 13.8 microg/g of dry weight, with green onion possessing the highest levels of CS (0.69 microg/g of dry weight), FT (1.99 microg/g of dry weight), and CT (13.85 microg/g of dry weight).