11 research outputs found
Epidermal Penetration of Gold Nanoparticles and Its Underlying Mechanism Based on Human Reconstructed 3D Episkin Model
Nanomaterials
are widely used in diverse aspects, and their translocation behavior
through the skin would be helpful in understanding the corresponding
exposure risks. To reveal how surface functionalization of nanoparticles
influences the skin penetration, three kinds of gold nanoparticles
(GNPs) with negatively, neutrally, and positively charged surfaces,
that is, cetyltrimethylammonium bromide-coated GNPs (CTAB@GNP), polyvinylpyrrolidone-coated
GNPs (PVP@GNP), and citrate-coated GNPs (Citrate@GNP), were studied
using human reconstructed 3D Episkin model. The measurement of Au
distribution in diverse layers of the Episkin model indicated that
all three GNPs could penetrate through the epidermis, wherein CTAB@GNP
with positive surface charges exhibited the highest efficiency in
skin penetration. The upward osmosis of the medium proteins confirmed
the occurrence of skin permeation induced by GNP treatment, and the
lipid network in the stratum corneum was also altered as the consequence
of GNP exposure. When compared to Citrate@GNP and PVP@GNP, CTAB@GNP
significantly compromised the tight junction of keratinocytes, causing
paracellular penetration of nanoparticles. The existence of cytoplasmic
gold showed the transcytosis pathway through endocytosis and exocytosis
processes was the main epidermic penetration behavior of the tested
GNPs. The study on GNP penetration process through the 3D Episkin
model has, on one hand, offered a promising approach to evaluate the
translocation process of nanoparticles across the skin, and, on the
other hand, provided mechanism explanation for diverse penetration
behaviors of GNPs with different surface charges. The findings herein
would be of great help in nanotechnology improvement and nanosafety
evaluation
Silica Nanoparticles Promote the Megakaryocyte Maturation and Differentiation: Potential Implications for Hematological Homeostasis
Silica nanoparticles (SiO2 NPs) have been
widely applied
in diverse areas, thus causing the extensive release through multiple
routes. Their toxicological effects, especially for the disturbance
in hematological homeostasis, have raised public concern. Considering
the detrimental role of excessive platelets in many cardiovascular
diseases, the regulation of platelet formation offers a unique aspect
for studying the blood compatibility of nanomaterials. In this study,
the effects of SiO2 NPs with four sizes (80, 120, 200,
and 400 nm) were investigated on the maturation and differentiation
of the megakaryocytes into platelets. The results showed that SiO2 NPs promoted megakaryocyte development as manifested by the
occurrence of irregular cell morphology, enlargement of cell size,
increases in DNA content and DNA ploidy, and formation of spore-like
protrusions. The expression of megakaryocyte-specific antigen (CD41a)
was up-regulated, due to SiO2 NP treatments. The correlation
analysis of SiO2 NP size with the above test bioindicators
showed that the smaller the SiO2 NPs were, the stronger
effects they induced. Moreover, exposure to SiO2 NPs induced
the up-regulation of both GATA-1 and FLI-1, while the transcriptional expressions of aNF-E2 and fNF-E2 remained unchanged. The significant
positive correlation of GATA-1 and FLI-1 with megakaryocytic maturation and differentiation suggested their
crucial roles in the SiO2 NP-promoted effect. The finding
herein provided new insight into the potential health risk of SiO2 NPs by perturbing the platelet-involved hematological homeostasis
Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway
Perfluorinated
iodine alkanes (PFIs) are used widely in the organic
fluorine industry. Increased production of PFIs has caused environmental
health concerns. To evaluate the potential endocrine-disrupting effect
of PFIs, we investigated the effects of perfluorooctyl iodide (PFOI)
on steroidogenesis in human adrenocortical carcinoma cells (H295R).
Levels of aldosterone, cortisol, 17β-estradiol, and testosterone
were measured in H295R culture medium upon treatment with perfluorooctanoic
acid (PFOA) and PFIs. Expression of 10 steroidogenic genes (<i>StAR</i>, <i>HMGR</i>, <i>CYP11A1</i>, <i>3βHSD2</i>, <i>17βHSD</i>, <i>CYP17</i>, <i>CYP21</i>, <i>CYP11B1</i>, <i>CYP11B2</i>, and <i>CYP19</i>) was measured by real-time polymerase
chain reaction. Levels of cyclic adenosine monophosphate (cAMP) and
adenylate cyclase (AC) activity were measured to understand the underlying
mechanism of steroidogenic perturbations. Levels of production of
aldosterone, cortisol, and 17β-estradiol were elevated significantly,
and the level of testosterone generation decreased upon treatment
with 100 ÎĽM PFOI. Similar to the effect induced by forskolin
(AC activator), expression of all 10 genes involved in the synthesis
of steroid hormones was upregulated significantly upon exposure to
100 ÎĽM PFOI. PFOA had no effect on steroid hormone production
or steroidogenic gene expression even though it is highly structurally
similar with PFOI. Therefore, the terminal -CF<sub>2</sub>I group
in PFOI could be a critical factor for mediation of steroidogenesis.
PFOI increased AC activity and cAMP levels in H295R cells, which implied
an underlying mechanism for the disturbance of steroidogenesis. These
data suggest that PFOI may act as an AC activator, thereby stimulating
steroidogenesis by activating a cAMP signaling pathway
Influence of the Surface Functional Group Density on the Carbon-Nanotube-Induced α‑Chymotrypsin Structure and Activity Alterations
Because of the special properties
of carbon nanotubes (CNTs), their applications have been introduced
to many fields. The biosafety of these emerging materials is of high
concern concomitantly. Because CNTs may initially bind with proteins
in biofluids before they exert biological effects, it is of great
importance to understand how the target proteins interact with these
exogenous nanomaterials. Here we investigated the interaction between
α-chymotrypsin (α-ChT) and carboxylized multiwalled CNTs
in a simulated biophysical environment utilizing the techniques of
fluorescence, UV–vis, circular dichroism spectroscopy, ζ
potential, atomic force microscopy, and bicinchoninic acid analysis.
It was demonstrated that CNTs interacted with α-ChT through
electrostatic forces, causing a decrement in the α-helix and
an increment in the β-sheet content of the protein. The protein
fluorescence was quenched in a static mode. The increase in the surface
modification density of CNTs enhanced the protein absorption and decreased
the enzymatic activity correspondingly. α-ChT activity inhibition
induced by CNTs with low surface modification density exhibited noncompetitive
characteristics; however, a competitive feature was observed when
CNTs with high surface modification density interacted with the protein.
An increase of the ionic strength in the reaction buffer may help
to reduce the interaction between CNTs and α-ChT because the
high ionic strength may favor the release of the protein from binding
on a CNT surface modified with functional groups. Accordingly, the
functionalization density on the CNT surface plays an important role
in the regulation of their biological effects and is worthy of concern
when new modified CNTs are developed
Renal Clearable Ag Nanodots for in Vivo Computer Tomography Imaging and Photothermal Therapy
Albumin-stabilized
Ag nanodots (ANDs) are prepared by a one-step
biomineralization method. The highly crystallized nanodots have ultrasmall
sizes (approximately 5.8 nm) and robust X-ray attenuation (5.7313
HU per mM Ag). The unlabeled ANDs are directly excreted from the body
via the urine after in vivo X-ray computer tomography (CT) imaging
application. ANDs could be used as CT imaging agents and effective
photothermal therapy agents. Tumor growth inhibition reaches 90.2%
after photothermal treatment with ANDs. ANDs are promising tools for
in vivo CT imaging and clearable near-infrared-triggered theranostic
agents
Sulfidation as a Natural Antidote to Metallic Nanoparticles Is Overestimated: CuO Sulfidation Yields CuS Nanoparticles with Increased Toxicity in Medaka (<i>Oryzias latipes</i>) Embryos
Sulfidation
is considered as a natural antidote to toxicity of
metallic nanoparticles (NPs). The detoxification contribution from
sulfidation, however, may vary depending on sulfidation mechanisms.
Here we present the dissolution–precipitation instead of direct
solid-state-shell mechanism to illustrate the process of CuO-NPs conversion
to CuS-NPs in aqueous solutions. Accordingly, the CuS-NPs at environmentally
relevant concentrations showed much stronger interference on Japanese
medaka (<i>Oryzias latipes</i>) embryo hatching than CuO-NPs,
which was probably due to elevated free copper ions released from
CuS-NPs, leading to significant increase in oxidative stress and causing
toxicity in embryos. The larval length was significantly reduced by
CuS-NPs, however, no other obviously abnormal morphological features
were identified in the hatched larvae. Co-introduction of a metal
ion chelator [ethylene diamine tetraacetic acid (EDTA)] could abolish
the hatching inhibition induced by CuS-NPs, indicating free copper
ions released from CuS-NPs play an important role in hatching interference.
This work documents for the first time that sulfidation as a natural
antidote to metallic NPs is being overestimated, which has far reaching
implications for risk assessment of metallic NPs in aquatic environment
Synthetic Phenolic Antioxidants Cause Perturbation in Steroidogenesis in Vitro and in Vivo
Synthetic phenolic antioxidants (SPAs)
are closely correlated with
human life due to their extensive usages, and increasing concerns
have been raised on their biosafety. The previous controversial findings
caused continuous debates on their potential endocrine disrupting
effects. In the present study, four commonly used SPAs, including
butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), <i>tert</i>-butyl hydroquinone (TBHQ) and 2,2′-methylenebisÂ(6-<i>tert</i>-butyl-4-methylphenol) (AO2246), were investigated for
their estrogenic effects, and the results from in vitro screening
assays showed SPAs themselves had negligible estrogen receptor binding
affinities. Nevertheless, significant increase in E<sub>2</sub> secretion
was observed in H295R cells treated with SPAs, especially for BHA.
The transcriptional levels of steroidogenic enzymes, including StAR,
3βHSD, CYP11B1, and CYP11B2 were up-regulated via the mediation
of protein kinase A (PKA) signaling pathway. In vivo experiment confirmed
that waterborne exposure to BHA disturbed E<sub>2</sub> and testosterone
(T) levels in zebrafish gonad, thus causing potential estrogenic effects
through the regulation of hypothalamic-pituitary–gonadal-liver
axis (HPGL-axis). Accordingly, this study has provided new insights
for SPA-induced endocrine disrupting effects. Considering the allowable
maximum level of individual BHA or in combination with TBHQ and BHT
in foodstuffs (200 mg kg<sup>–1</sup>), the perturbation in
steroidogenesis observed for relatively low concentrations of SPAs
would need more public attention
Permission to Enter Cell by Shape: Nanodisk vs Nanosphere
Changing polystyrene nanoparticles from three-dimensional
spherical
shape to two-dimensional disk shape promotes their cell surface binding
with significant reduction of cell uptake. As a result of lower cell
uptake, nanodisks show very little perturbations on cell functions
such as cellular ROS generation, apoptosis and cell cycle progression
compared to nanospheres. Therefore, disk-shaped nanoparticles may
be a promising template for developing cell membrane-specific and
safer imaging agents for a range of biomedical applications such as
molecular imaging, tissue engineering, cell tracking, and stem cell
separation
Structure-Dependent Hematological Effects of Per- and Polyfluoroalkyl Substances on Activation of Plasma Kallikrein–Kinin System Cascade
Per-
and polyfluoroalkyl substances (PFASs) are a global concern
because of their ubiquitous occurrence and high persistence in human
blood, and increasing amounts of unidentified fluorinated compounds
are now becoming new exposure issues. This study aims to investigate
the structure-related effects of PFASs on the activation of the plasma
kallikrein-kinin system (KKS). The effects of 20 PFASs and the related
long-chain aliphatic compounds were screened, and their binding affinities
for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were
evaluated by molecular docking analysis. PFASs were demonstrated to
activate the KKS in a structure-dependent mode. More specifically,
PFASs with longer carbon chain length, higher fluorine atom substitution
degree, and terminal acid group exhibited relatively higher activities
in activating the KKS. The binding affinities of PFASs with FXII determined
their capabilities for inducing KKS activation. The alternative binding
modes of PFASs with FXII, together with van der Waals and hydrogen
bonds, specifically accommodated the distinctive chemical structures.
To our knowledge, PFASs, for the first time, were found to induce
the activation of the KKS in plasma, and their chemical structure-related
effects would be extremely important for risk assessment on emerging
PFASs in addition to the listing in Stockholm Convention
Graphene Enhances Cellular Proliferation through Activating the Epidermal Growth Factor Receptor
Graphene
has promising applications in food packaging, water purification,
and detective sensors for contamination monitoring. However, the biological
effects of graphene are not fully understood. It is necessary to clarify
the potential risks of graphene exposure to humans through diverse
routes, such as foods. In the present study, graphene, as the model
nanomaterial, was used to test its potential effects on the cell proliferation
based on multiple representative cell lines, including HepG2, A549,
MCF-7, and HeLa cells. Graphene was characterized by Raman spectroscopy,
particle size analysis, atomic force microscopy, and transmission
electron microscopy. The cellular responses to graphene exposure were
evaluated using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide, and alamarBlue assays. Rat cerebral astrocyte cultures, as
the non-cancer cells, were used to assess the potential cytotoxicity
of graphene as well. The results showed that graphene stimulation
enhanced cell proliferation in all tested cell cultures and the highest
elevation in cell growth was up to 60%. A western blot assay showed
that the expression of epidermal growth factor (EGF) was upregulated
upon graphene treatment. The phosphorylation of EGF receptor (EGFR)
and the downstream proteins, ShC and extracellular regulating kinase
(ERK), were remarkably induced, indicating that the activation of
the mitogen-activated protein kinase (MAPK)/ERK signaling pathway
was triggered. The activation of PI3 kinase p85 and AKT showed that
the PI3K/AKT signaling pathway was also involved in graphene-induced
cell proliferation, causing the increase of cell ratios in the G2/M
phase. No influences on cell apoptosis were observed in graphene-treated
cells when compared to the negative controls, proving the low cytotoxicity
of this emerging nanomaterial. The findings in this study revealed
the potential cellular biological effect of graphene, which may give
useful hints on its biosafety evaluation and the further exploration
of the bioapplication