Exposure to Valproic acid (VPA) resulted in alterations in the expression of angiogenic genes (NRP-1, VEGFA, VEGFR-2 and sFlt1) and histological modifications in the placenta of mice (Mus musculus).

Valproic acid (VPA), an anti-epileptic drug (AED), has been reported to exhibit anti-angiogenic properties. This study aimed to examine the impact of VPA on the expression of NRP-1 and additional angiogenic factors, as well as angiogenesis, in mouse placenta. Pregnant mice were divided into four groups: control (K), solvent control (KP), VPA treatment at a dose of 400 mg/kg body weight (BW) (P1), and VPA treatment at a dose of 600 mg/kg BW (P2). The mice were subjected to daily treatment via gavage from embryonic day (E) 9 to E14 and E9 to E16. Histological analysis was performed to evaluate Microvascular Density (MVD) and percentage of the placental labyrinth area. In addition, a comparative analysis of Neuropilin-1 (NRP-1), vascular endothelial growth factor (VEGFA), vascular endothelial growth factor receptor (VEGFR-2), and soluble (sFlt1) expression was conducted in relation to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The results of the MVD analysis and percentage of labyrinth area in the E14 and E16 placentas indicated that the treated groups were significantly lower than the control group. The relative expression levels of NRP-1, VEGFA, and VEGFR-2 in the treated groups were lower than those in the control group at E14 and E16. Meanwhile, the relative expression of sFlt1 in the treated groups at E16 was significantly higher than in the control group. Changes in the relative expression of these genes inhibit angiogenesis regulation in the mouse placenta, as evidenced by reduced MVD and a smaller percentage of the labyrinth area.

Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold.

Guanine-quadruplex-based CpG oligodeoxynucleotides (G4 CpG ODNs) have been developed as potent immunostimulatory agents with reduced sensitivity to nucleases. We designed new monomeric G4 ODNs with an antiparallel topology using antiparallel type duplex/G4 ODNs as robust scaffolds, and we characterized their topology and effects on cytokine secretion. Based on circular dichroism analysis and quantification of mRNA levels of immunostimulatory cytokines, it was found that monomeric antiparallel G4 CpG ODNs containing two CpG motifs in the first functional loop, named G2.0.0, could maintain antiparallel topology and generate a high level of immunostimulatory cytokines in RAW264 mouse macrophage-like cell lines. We also found that the flanking sequence in the CpG motif altered the immunostimulatory effects. Gc2c.0.0 and Ga2c.0.0 are monomeric antiparallel G4 CpG ODNs with one cytosine in the 3' terminal and one cytosine/adenine in the 5' terminal of CpG motifs that maintained the same resistance to degradation in serum as G2.0.0 and improved interleukin-6 production in RAW264 and bone marrow-derived macrophages. The immunostimulatory activity of antiparallel G4 CpG ODNs is superior to that of linear natural CpG ODNs. These results provide insights for the rational design of highly potent CpG ODNs using antiparallel G4 as a robust scaffold.

Bioprospecting of Turbinaria Macroalgae as a Potential Source of Health Protective Compounds.

The present study aims to focus on the bioprospecting of marine macroalgae of Turbinaria species, plenteous biomass of the world ocean. Three types of solvents, i.e., H2 O, MeOH/H2 O (80:20, v/v) and hexane/i-PrOH (50:50, v/v), were used for extraction. Both the biological activity and the pattern of present chemicals were characterized. For the cell proliferation assay, the human embryonic kidney 293 cells, cervix/breast/pancreatic adenocarcinoma, and osteosarcoma cells were used. For the antioxidant activity determination, both intracellular assay with human embryonic kidney and cervix adenocarcinoma cells, as well as the biochemical DPPH test, were employed. To complete the information about macroalgae composition, organic compounds were characterized by the liquid chromatography coupled with high resolution tandem mass spectrometry. Attention was concentrated mainly on the lipidomic profile characterization. In spite the fact that any significant antiproliferative effect was not observed for cancer cells, both the Turbinaria species were shown to be good protectors against the oxidative stress of the non-cancer cells. Most of the antioxidants were determined in the hexane/i-PrOH extract. As regards the lipids identified, most of them belonged to the triacylglycerols followed by sphingomyelins, diacylglycerols, and polar (lyso)phospholipids. Additionally to fatty acids with 14, 16 and 18 carbons, also those with odd carbon numbers were frequently present.