Heat Shock Alters Mesenchymal Stem Cell Identity and Induces Premature Senescence.

Heat stress can have a serious impact on the health of both humans and animals. A major question is how heat stress affects normal development and differentiation at both the cellular and the organism levels. Here we use an in vitro experimental system to address how heat shock treatment influences the properties of bovine mesenchymal stem cells (MSCs)-multipotent progenitor cells-which are found in most tissues. Because cattle are sensitive to harsh external temperatures, studying the effects of heat shock on MSCs provides a unique platform to address cellular stress in a physiologically relevant model organism. Following isolation and characterization of MSCs from the cow's umbilical cord, heat shock was induced either as a pulse (1 h) or continuously (3 days), and consequent effects on MSCs were characterized. Heat shock induced extensive phenotypic changes in MSCs and dramatically curtailed their capacity to proliferate and differentiate. These changes were associated with a partial arrest in the G1/S or G2/M checkpoints. Furthermore, MSCs lost their ability to resolve the inflammatory response of RAW macrophages in coculture. A possible explanation for this loss of function is the accumulation of reactive oxygen species and malfunction of the mitochondria in the treated cells. Heat shock treatments resulted in stress-induced premature senescence, affecting the MSCs' ability to proliferate properly for many cell passages to follow. Exposure to elevated external temperatures leads to mitochondrial damage and oxidative stress, which in turn conveys critical changes in the proliferation, differentiation, and immunomodulatory phenotype of heat-stressed MSCs. A better understanding of the effect of heat shock on humans and animals may result in important health and economic benefits.

Pharmacokinetics in Plants: Carbamazepine and Its Interactions with Lamotrigine.

Carbamazepine and lamotrigine prescribed antiepileptic drugs are highly persistent in the environment and were detected in crops irrigated with reclaimed wastewater. This study reports pharmacokinetics of the two drugs and their metabolites in cucumber plants under hydroponic culture, testing their uptake, translocation, and transformation over 96 h in single and bisolute systems at varying pH. Ruling out root adsorption and transformations in the nutrient solution, we demonstrate that carbamazepine root uptake is largely affected by the concentration gradient across the membrane. Unlike carbamazepine, lamotrigine is adsorbed to the root and undergoes ion trapping in root cells thus its translocation to the shoots is limited. On the basis of that, carbamazepine uptake was not affected by the presence of lamotrigine, while lamotrigine uptake was enhanced in the presence of carbamazepine. Transformation of carbamazepine in the roots was slightly reduced in the presence of lamotrigine. Carbamazepine metabolism was far more pronounced in the shoots than in the roots, indicating that most of the metabolism occurs in the leaves, probably due to higher concentration and longer residence time. This study indicates that the uptake of small nonionic pharmaceuticals is passive and governed by diffusion across the root membrane.

Insights into the uptake processes of wastewater-borne pharmaceuticals by vegetables.

An increasing number of reports on plant uptake of pharmaceutical compounds (PCs) have been recently published, raising concerns of human exposure through dietary intake. In this study, PC uptake and translocation were evaluated in cucumber and tomato plants to elucidate the effects of PC physicochemical properties, soil type, and irrigation-water quality. Nonionic PCs were taken up and accumulated at higher levels in plants grown in soils of lower organic matter and clay content. While the concentration of most PCs in cucumber and tomato leaves were of similar order, their concentrations in the tomato fruit were much lower than in the cucumber fruit. This is related to differences in fruit physiology. Our data suggest that irrigation with treated wastewater reduces the bioavailability of acidic PCs for uptake by cucumber plants as compared to fresh water irrigation. This study sheds light on factors affecting the uptake of PCs by crops irrigated with treated wastewater, the governing role of PCs' physicochemical properties along with the physiological nature of the plant, soil properties and water quality that together determine uptake, translocation, and accumulation within plant organs. Occurrence of metabolites in plant suggests that PC metabolism has to be evaluated to reveal the total uptake.