Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis

BACKGROUND: Given that the effects of ultrafine fractions (<0.1 μm) on ischemic heart diseases (IHD) and other cardiovascular diseases are gaining attention, this study is aimed to explore the influence of silica nanoparticles (SiNPs)-induced autophagy on endothelial cell homeostasis and angiogenesis. METHODS AND RESULTS: Ultrastructural changes of autophagy were observed in both vascular endothelial cells and pericytes in the heart of ICR mice by TEM. Autophagic activity and impaired angiogenesis were further confirmed by the immunohistochemistry staining of LC3 and VEGFR2. In addition, the immunohistochemistry results showed that SiNPs had an inhibitory effect on ICAM-1 and VCAM-1, but no obvious effect on E-selectin in vivo. The disruption of F-actin cytoskeleton occurred as an initial event in SiNPs-treated endothelial cells. The depolarized mitochondria, autophagic vacuole accumulation, LC3-I/LC3-II conversion, and the down-regulation of cellular adhesion molecule expression were all involved in the disruption of endothelial cell homeostasis in vitro. Western blot analysis indicated that the VEGFR2/PI3K/Akt/mTOR and VEGFR2/MAPK/Erk1/2/mTOR signaling pathway was involved in the cardiovascular toxicity triggered by SiNPs. Moreover, there was a crosstalk between the VEGFR2-mediated autophagy signaling and angiogenesis signaling pathways. CONCLUSIONS: In summary, the results demonstrate that SiNPs induce autophagic activity in endothelial cells and pericytes, subsequently disturb the endothelial cell homeostasis and impair angiogenesis. The VEGFR2-mediated autophagy pathway may play a critical role in maintaining endothelium and vascular homeostasis. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by nano-sized particles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-014-0050-8) contains supplementary material, which is available to authorized users

Toxic Effects of Silica Nanoparticles on Zebrafish Embryos and Larvae

Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 μg/mL) during 4-96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 μg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 μg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior. © 2013 Duan et al.published_or_final_versio

Characteristics of Block by Pb 2ϩ of Function of Human Neuronal L-, N-, and R-Type Ca 2ϩ Channels Transiently Expressed in Human Embryonic Kidney 293 Cells

ABSTRACT Lead (Pb 2ϩ ) is a well-known inhibitor of voltage-dependent Ca 2ϩ channels in their native environments in several types of cells. However, its effects on discrete Ca 2ϩ channel phenotypes in isolation have not been well studied. We compared how specific subtypes of human neuronal high-voltage-activated Ca 2ϩ channels were affected by acute exposure to Pb 2ϩ . Expression cDNA clones of human ␣ 1C , ␣ 1B , or ␣ 1E subunit genes encoding neuronal L-, N-, and R-subtypes of Ca 2ϩ channels, respectively, along with a constant ␣ 2 ␦ and ␤ 3 subunits were transfected into human embryonic kidney 293 cells. Currents through the respective transiently expressed channels were measured using wholecell recording techniques with Ba 2ϩ (20 mM) as charge carrier. Extracellular bath applications of Pb 2ϩ significantly reduced current amplitude through all three types of Ca 2ϩ channels in a concentration-dependent manner. The order of potency was: ␣ 1E (IC 50 ϭ 0.10 M), followed by ␣ 1C (IC 50 ϭ 0.38 M) and ␣ 1B (IC 50 ϭ 1.31 M). Pb 2ϩ -induced perturbation of function of ␣ 1C and ␣ 1B containing Ca 2ϩ channels was more easily reversed than for ␣ 1E -containing Ca 2ϩ channels after washing with Pb 2ϩ free solution. The current-voltage relationships were not altered after 3-min exposure to Pb 2ϩ for any of the three types. However, the steady-state inactivation relationships were shifted to more negative potentials for channels containing ␣ 1B and ␣ 1E subunits, but not for those containing ␣ 1C subunits. Pb 2ϩ accelerated the inactivation time of current in all three subtypes of Ca 2ϩ channels in a concentration-and voltage-dependent manner. Therefore, different subtypes of Ca 2ϩ channels exhibit differential susceptibility to Pb 2ϩ even when expressed in the same cell type. Current expressed by ␣ 1E -containing channels is more sensitive to Pb 2ϩ than that expressed by ␣ 1C -or ␣ 1B -containing channels. Several Ca 2ϩ channel phenotypes are quite sensitive to the inhibitory action of Pb 2ϩ . Furthermore, it seems that Pb 2ϩ is more likely to combine with Ca 2ϩ channels in the closed state

Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment

The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment

Brominated flame retardants (BFRs) in sediment from a typical e-waste dismantling region in Southern China: Occurrence, spatial distribution, composition profiles, and ecological risks

Our study evaluated the current occurrence, composition, and spatial distribution of eight congeners of polybrominated diphenyl ethers (PBDEs) and seven novel brominated flame retardants (NBFRs) in sediment from Guiyu, a typical e-waste dismantling region in China. PBDEs levels ranged from 0.345 to 401,000 ng/g dw and NBFRs levels ranged from 0.581 to 73,100 ng/g dw. Almost all sediment samples contained high levels of BDE-209 and DBDPE, and the ratio of DBDPE/BDE-209 in sediments ranged from 0.0814 to 2.80 (mean: 0.879). The concentration and composition profiles for BFRs in sediments from both mainstream and tributaries of two major rivers in Guiyu reach (and adjacent downstream locations) differed significantly from those far from Guiyu town. Whereas the high presence of BFRs in Guiyu reflected the historical crude e-waste dismantling activities in the region; the locations far from Guiyu town were likely to receive BFRs from atmospheric deposition, not originated from the region, as BFRs in water-sediment are known to be able to migrate a limited distance along the river. Ecological risk assessment revealed that the low brominated congeners of PBDEs and BDE-209 posed an unacceptable risk to the sedimentary life at multiple locations. Our results updated our knowledge of BFRs contamination in Guiyu, suggesting the necessity of continuous source monitoring, control procedures, and sediment cleanup for BFRs

Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy

Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapyHypertension is a key risk factor in the progression of cardiovascular disease (CVD). Dyslipidemia, a strong predictor of CVD, frequently coexists with hypertension. Therefore, the control of hypertension and dyslipidemia may help reduce CVD morbidity and mortality. In the present study, the therapeutic effects of antihypertensive agents on blood pressure control and plasma lipid metabolism were evaluated. The plasma lipid profiles of patients with treated (n = 25) or untreated (n = 30) essential hypertension as well as of subjects with normotension (n = 28) were analyzed using liquid chromatography mass spectrometry. Principal component analysis of the lipidomics data revealed distinct clusters among studied subjects across three human populations. Phosphatidylcholines and triacylglycerols (TG) dominated the pattern of hypertension-influenced plasma lipid metabolism. Discriminatory lipid metabolites were analyzed using one-way analysis of variance followed by a post hoc multiple comparison correction. TG lipid class was significantly increased by 49.0% (p < 0.001) in hypertensive vs. normotensive groups while tended to decrease (-21.2%, p = 0.054) in hypertensive patients after treatment. Total cholesteryl esters were significantly decreased by -16.9% (p < 0.001) in hypertensive patients after treatment. In particular, a large number of individual neutral lipid species were significantly elevated in hypertensive subjects but significantly decreased after treatment with antihypertensive agents. The present study applied, for the first time, a systems biology based lipidomics approach to investigate differentiation among plasma lipid metabolism of patients with treated/untreated essential hypertension and subjects with normotension. Our results demonstrate that antihypertensive medications to lower blood pressure of hypertensive patients to target levels produced moderate plasma lipid metabolism improvement of patients with hypertension

Influence of zinc phthalocyanines on photoelectrical properties of hydrogenated amorphous silicon

Composites consisting of hydrogenated amorphous silicon (a-Si: H, inorganic) and zinc phthalocyanine (ZnPc, organic) were prepared by vacuum evaporation of ZnPc and sequential deposition amorphous silicon via plasma enhanced chemical vapor deposition (PECVD). The optical and electrical properties of the composite film have been investigated. The results demonstrate that ZnPc can endure the temperature and bombardment of the PECVD plasma and photoconductivity of the composite film was improved by 89.9% compared to pure a-Si: H film. Electron mobility-lifetime products μτ of the composite film were increased by nearly one order of magnitude from 6.96 × 10~(-7) to 5.08 × 10~(-6) cm~2/V. Combined with photoconductivity spectra of the composites and pure a-Si: H, we tentatively elucidate the improvement in photoconductivity of the composite film

Slow-Release Drug Deliver System with Polylactic Acid Hydrogels in Prevention of Tracheal Wall Fibroplasia

Objective: To compare the effect of slow-release mitomycin C (MMC) and dexamethasone sodium phosphate (DSP) to polylactic acid (PLA) hydrogels on the prevention of tracheal wall fibroplasia. Methods: The release speed of MMC and DSP mixed with PLA hydrogels was determined in vitro and in vivo. The rabbit model of tracheal wall fibroplasia was made through scratching the tracheal wall. Forty-two rabbits were divided into 7 groupsand 0.2ml PLA hydrogels containing different doses of MMC and DSP mixed with spongia gelatinosa composite were put in semicircular silicone tubes and then were placed on the wound surface of the scratched tracheal wall. An air embolism killed each animal 4 weeks later. The histology of the specimens was studied. Results: The 1mg MMC and 2mg DSP PLA hydrogels could release over 35 days and 28 days respectively in vitro. The tracheal wall fibroplasia in DSP and MMC groups, except the 0.1mg MMC group, was thinner than that in the control group (P0.05). Conclusions: Both MMC/PLA and DSP/PLA hydrogels can inhibit fibroplasia of the tracheal wall and it can be coated in a Poly L-lactide-co and ndash;glycolide (PLGA) scaffold for treating laryngeal-tracheal stenosis in future. [Arch Clin Exp Surg 2012; 1(1.000): 1-7