Cardiovascular toxicity assessment of poly (ethylene imine)- based cationic polymers on zebrafish model

<p>Poly(ethylene imine)s (PEIs) have gained enormous attention in designing novel drug delivery systems for cancer treatment. High molecular weight of PEIs such as PEI 25 kD are promising for their drug carrying capacity. However, increased molecular weight is associated with toxicity. Currently, the toxicity evaluation of PEIs is mainly focused on the culture cell models, with very few studies investigating the risk assessment <i>in vivo</i>. Herein, the systemic evaluation of branched PEI 25 kD and PEI-CyD (PC) composed of low molecular PEI (Mw 600) and β-cyclodextrin (β-CyD) is performed in zebrafish model and endothelial cells. Our finding indicate that exposure of PC and PEI 25 kD can induce high mortality rate, shorten hatching time, promote malformations and cell apoptosis of zebrafish embryos in a dose-dependent manner. Most significantly, the cationic polymer PC and PEI 25 kD can decrease heart rate of zebrafish embryos and down-regulate the expression of heart development-related genes, which demonstrate their cardiovasculature toxicity. In this case, we further investigate the effect of PC on endothelial cells. Indeed, PC can induce endothelial cells dysfunction, including oxidative stress and apoptosis which are involved in cardiovascular diseases. These fundamental studies provide valuable insights into the biocompatible evaluation of PEI based drug carriers.</p

The clock gene transcripts in <i>M. aeruginosa</i> under light and dark conditions after H₂O₂ treatment.

<p>The shaded areas correspond to the dark period. Symbols represent mean ± SEM of triplicate cultures. The mRNA amount of all examined genes is normalized to 16S rDNA. The open circle corresponds to the control treatment; the filled circle corresponds to the L0 treatment; the filled square corresponds to the D0 treatment. A, The effect of H₂O₂ on the <i>kaiA</i> circadian transcript; B, the effect of H₂O₂ on the <i>kaiB</i> circadian transcript; C: the effect of H₂O₂ on the <i>kaiC</i> circadian transcript; D: the effect of H₂O₂ on the <i>sasA</i> circadian transcript.</p

The change of microcystin content in water after oxidation by H₂O₂ for various time periods.

<p>The change of microcystin content in water after oxidation by H₂O₂ for various time periods.</p

The intracellular microcystin content of <i>M. aeruginosa</i> under light and dark conditions after H₂O₂ treatment.

<p>The shaded areas correspond to the dark period. The symbols represent the mean ± SEM of triplicate cultures. The filled circle corresponds to the L0 treatment; the open circle corresponds to the control treatment; the filled square corresponds to the D0 treatment.</p

Photosynthesis-related gene transcripts in <i>M. aeruginosa</i> under light and dark conditions after H₂O₂ treatment.

<p>The shaded areas correspond to the dark period. Symbols represent mean ± SEM of triplicate cultures. The mRNA amount of all examined genes is normalized to 16S rDNA. The open circle corresponds to the control treatment; the filled circle corresponds to the L0 treatment; the filled square corresponds to the D0 treatment. A: The effect of H₂O₂ on <i>psaB</i> circadian transcript; B: the effect of H₂O₂ on the <i>psbD1</i> circadian transcript; C: the effect of H₂O₂ on the <i>rbcL</i> circadian transcript.</p

Effects of H₂O₂ on the inhibition of <i>M. aeruginosa</i> growth.

<p>Effects of H₂O₂ on the inhibition of <i>M. aeruginosa</i> growth.</p

Inhibitory effects of H₂O₂ on Chl a, PE, PC and APC levels in <i>M. aeruginosa</i> for 24 h.

<p>Inhibitory effects of H₂O₂ on Chl a, PE, PC and APC levels in <i>M. aeruginosa</i> for 24 h.</p

Growth of <i>M. aeruginosa</i> that was cultured with H₂O₂ in the first 24 h.

<p>The shaded areas correspond to the dark period. Symbols represent mean ± SEM of triplicate cultures. The open circle corresponds to the control treatment; the filled circle corresponds to the L0 treatment; the filled square corresponds to the D0 treatment.</p

Analysis of Enantioselective Biochemical, Physiological, and Transcriptional Effects of the Chiral Herbicide Diclofop Methyl on Rice Seedlings

Diclofop methyl (DM) is a chiral herbicide that is widely used as a racemic mixture. This study analyzed the enantioselective effects of <i>R-</i> and <i>S</i>-DM on rice at the physiological and molecular levels. DM exerts an enantioselective effect on rice growth, reactive oxygen substance (ROS) formation, and antioxidant gene expression, with <i>R</i>-DM acting as a more potent stressor than <i>S</i>-DM. An analysis of chlorophyll fluorescence demonstrated that photosynthesis process was more strongly inhibited by <i>R</i>-DM than by <i>S</i>-DM. Microarray results showed that many metabolic pathways, including starch and sucrose metabolism, oxidative phosphorylation, and amino acid biosynthesis and metabolism, were affected by DM in an enantioselective manner. These results suggest that <i>R-</i>DM is more active to plant growth than <i>S</i>-DM and that this activity is induced not only by repression of fatty acid synthesis but also by <i>R-</i>DM affecting the transcription of genes in other metabolic pathways in an enantioselective manner

Effects of altered photoperiod on circadian clock and lipid metabolism in rats

<p>Disruption of circadian clock timekeeping due to changes in the photoperiod enhances the risk of lipid metabolism disorders and metabolic syndrome. However, the effects of altered photoperiods on the circadian clock and lipid metabolism are not well understood. To explore the effects of altered photoperiods, we developed a rat model where rats were exposed to either short-day or long-day conditions. Our findings demonstrated that altered photoperiods mediated circadian clocks by partly disrupting rhythmicity and shifting phase values of clock genes. We also showed that compared to long-day conditions, rats under short-day conditions exhibited more photoperiodic changes in a variety of physiological outputs related to lipid metabolism, such as significant increases in serum triglyceride (TG), high-density lipoprotein, and leptin levels, as well as increased body weight, fat:weight ratio, and hepatic TG levels. These increments were gained possibly through upregulated expression of forkhead box O1 (<i>FoxO1</i>), which partly mediates the expression of peroxisome proliferator-activated receptorα (<i>PPARα</i>) to increase the expression of phosphoenolpyruvate carboxykinase (<i>PEPCK</i>), peroxisome proliferator-activated receptor-g coactivator-1β (<i>PGC1β</i>), and fatty acid synthase (<i>Fas</i>n). In addition, the oscillation rhythms of <i>FoxO1, PEPCK, PGC1β</i>, and <i>Fasn</i> expression levels in the livers of rats exposed to a short-day photoperiod were more robust than those exposed to a long-day photoperiod. These findings suggest that a change in photoperiod can partly disrupt the circadian rhythmcity of clock genes, impair lipid metabolism, and promote obesity.</p