Differential Effect of Simulated Microgravity on the Cellular Uptake of Small Molecules.

The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours.

Valproic acid reprograms the metabolic aberration of cisplatin treatment via ALDH modulation in triple-negative breast cancer cells.

We recently demonstrated that the histone deacetylase inhibitor valproic acid (VPA) reprograms the cisplatin-induced metabolome of triple-negative breast cancer (TNBC) cells, including a shift in hexose levels. Accordingly, here, we tested the hypothesis that VPA alters glucose metabolism in correlation with cisplatin sensitivity. Two TNBC cell lines, MDA-MB-231 (a cisplatin-resistant line) and MDA-MB-436 (a cisplatin-sensitive line), were analyzed.

Effects of antiseizure medications on placental cells: Focus on heterodimeric placental carriers.

Objective: Appropriate placental nutrient transfer is essential for optimal fetal development. We have previously shown that antiseizure medications (ASMs) can alter the expression of placental carriers for folate and thyroid hormones. Here we extended our analysis to heterodimeric carriers that mediate the placental uptake of amino acids and antioxidant precursors.

Antiseizure medications and fetal nutrients: Effects on choline transporters in a human placental cell line.

Objective: Many nutrients essential to the fetus and for proper function of the placenta itself cannot freely diffuse across membrane barriers, and their transplacental transfer depends on transporters. Our previous studies provided evidence for altered expression of transporters for folic acid in trophoblasts exposed to antiseizure medications (ASMs). The goal of the current study was to explore the effects of older and newer ASMs on the expression and function of uptake transporters for choline, which interacts with folate at pathways for methyl group donation.

The effects of valproic acid on early pregnancy human placentas: Pilot ex vivo analysis in cultured placental villi.

Valproic acid is an established structural and neurodevelopmental teratogen. Recently, we demonstrated that valproate alters the barrier function of perfused term human placentas. Here, we conducted a pilot study to evaluate the effects of subchronic valproate exposure on carrier expression in cultured placental villous explants from early human pregnancies.

Lacosamide at therapeutic concentrations induces histone hyperacetylation in vitro.

Inhibition of histone deacetylases (HDACs) and subsequent hyperacetylation of histone proteins lead to altered gene expression associated with therapeutic drug effects, but also with teratogenicity. The only US Food and Drug Administration (FDA)-approved antiepileptic drug that has been consistently shown to induce histone hyperacetylation is valproic acid. More recently, lacosamide was reported to interfere with histone modifications, but histone hyperacetylation was not demonstrated.

The Placental Barrier: the Gate and the Fate in Drug Distribution.

Optimal development of the embryo and the fetus depends on placental passage of gases, nutrients, hormones, and waste products. These molecules are transferred across the placenta via passive diffusion, carrier-mediated cellular uptake and efflux, and transcytosis pathways. The same mechanisms additionally control the rate and extent of transplacental transfer of drugs taken by the pregnant mother.