"Assessing exposure of printing factory workers in thailand to selected heavy metals using urine and hair as non-invasive matrices".

BACKGROUND: There are few thorough studies on the extent and inter-element relationships of heavy metal contamination in printing factory workers, especially in developing countries. The objective of this study was to determine the levels of eight heavy metals, including arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), cobalt (Co), lead (Pb), mercury (Hg), and manganese (Mn), in urine and scalp hair of printing industry workers, and assess inter-element correlations. METHODS: We examined a total of 85 urine samples and 85 scalp hair samples (3 cm hair segments taken from near the scalp) in 85 printing workers from a printing house in Bangkok, Thailand. We used an interviewer-administered questionnaire about participants' printing techniques, work characteristics, and work environment. Urine and scalp hair samples were analyzed for levels of each element using the inductively coupled plasma optical emission spectrometry (ICP-OES) technique. RESULTS: As, Cd, Cr, Ni, Pb were detected in urine with the geometric mean concentration range of 0.0028-0.0209 mg/L, and Hg, Pb, Ni, Cd, Co, Mn, Cr were detected in hair samples (0.4453-7.165 mg/kg dry weight) of printing workers. The geometric mean Ni level was significantly higher in the urine of production line workers than back-office personnel (0.0218 mg/L vs. 0.0132 mg/L; p = 0.0124). The other elements did not differ significantly between production line and back-office workers in either urine or hair. There was also a strong, statistically significant positive correlation between Ni and Co levels in hair samples of workers (r = 0.944, p < 0.0001). CONCLUSIONS: Average concentrations of most of the metals in urine and hair of printing workers were found to be above the upper reference values. The significantly higher concentrations of Ni in production line workers might be due to more exposure to printed materials. A strong inter-element correlation between Ni and Co in hair samples can increase stronger health effects and should be further investigated. This study reveals possible dependencies and impact interactions of heavy metal exposure in printing factory workers.

Gold Nanoparticles Affect Pericyte Biology and Capillary Tube Formation.

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-ß (PDGFR-ß) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-ß mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-ß mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.

Effect of Gold Nanoparticles on the TLR2-Mediated Inflammatory Responses Induced by Leptospira in TLR2-Overexpressed HEK293 Cells.

Leptospira infection can cause potential hazards to human health by stimulating inflammation, which is mediated mainly through the Toll-like receptor 2 (TLR2) pathway. Gold nanoparticles (AuNPs) are promising for medical applications, as they display both bioinert and noncytotoxic characteristics. AuNPs have been shown to have the ability to modify immune responses. To understand the in vitro immunomodulatory effect of AuNPs in a Leptospira infection model, the activation of TLR2 expression was examined in HEK-Blue-hTLR2 cells treated with Leptospira serovars and/or AuNPs (10 and 20 nm). The ability of AuNPs to modulate an inflammatory response induced by Leptospira was examined in terms of transcript expression level modulation of three proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß and IL-6) using two-stage quantitative real-time reverse transcriptase PCR. The results revealed that the administration of 10 nm AuNPs could augment the Leptospira-induced TLR2 signaling response and upregulate the expression of all three cytokine gene transcripts, whereas the 20 nm AuNPs attenuated the TLR2 activation and expression of proinflammatory cytokines. This indicates that AuNPs can modulate inflammatory parameters in Leptospira infection and different-sized AuNPs had different immunomodulatory functions in this model.

N-acetylcysteine reverses the decrease of DNA methylation status caused by engineered gold, silicon, and chitosan nanoparticles.

Introduction: Engineered nanoparticles (ENPs) are one of the most widely used types of nanomaterials. Recently, ENPs have been shown to cause cellular damage by inducing ROS (reactive oxygen species) both directly and indirectly, leading to the changes in DNA methylation levels, which is an important epigenetic mechanism. In this study, we investigated the effect of ENP-induced ROS on DNA methylation. Materials and methods: Human embryonic kidney and human keratinocyte (HaCaT) cells were exposed to three different types of ENPs: gold nanoparticles, silicon nanoparticles (SiNPs), and chitosan nanoparticles (CSNPs). We then evaluated the cytotoxicity of the ENPs by measuring cell viability, morphology, cell apoptosis, cell proliferation, cell cycle distribution and ROS levels. Global DNA methylation levels was measured using 5-methylcytosine immunocytochemical staining and HPLC analysis. DNA methylation levels of the transposable elements, long interspersed element-1 (LINE-1) and Alu, were also measured using combined bisulfite restriction analysis technique. DNA methylation levels of the TEs LINE-1 and Alu were also measured using combined bisulfite restriction analysis technique. Results: We found that HaCaT cells that were exposed to SiNPs exhibited increased ROS levels, whereas HaCaT cells that were exposed to SiNPs and CSNPs experienced global and Alu hypomethylation, with no change in LINE-1 being observed in either cell line. The demethylation of Alu in HaCaT cells following exposure to SiNPs and CSNPs was prevented when the cells were pretreated with an antioxidant. Conclusion: The global DNA methylation that is observed in cells exposed to ENPs is associated with methylation of the Alu elements. However, the change in DNA methylation levels following ENP exposure is specific to particular ENP and cell types and independent of ROS, being induced indirectly through disruption of the oxidative defense process.

Molecular and Morphological Evidence of Hepatotoxicity after Silver Nanoparticle Exposure: A Systematic Review, In Silico, and Ultrastructure Investigation.

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

Copper Oxide Nanoparticles Cause a Dose-Dependent Toxicity via Inducing Reactive Oxygen Species in Drosophila.

Copper oxide nanoparticles (CuONPs) have attracted considerable attention, because of their biocide potential and capability for optical imaging, however CuONPs were shown to be highly toxic in various experimental model systems. In this study, mechanism underlying CuONP-induced toxicity was investigated using Drosophila as an in vivo model. Upon oral route of administration, CuONPs accumulated in the body, and caused a dose-dependent decrease in egg-to-adult survivorship and a delay in development. In particular, transmission electron microscopy analysis revealed CuONPs were detected inside the intestinal epithelial cells and lumen. A drastic increase in apoptosis and reactive oxygen species was also observed in the gut exposed to CuONPs. Importantly, we found that inhibition of the transcription factor Nrf2 further enhances the toxicity caused by CuONPs. These observations suggest that CuONPs disrupt the gut homeostasis and that oxidative stress serves as one of the primary causes of CuONP-induced toxicity in Drosophila.

Cytoprotective effect of glutaraldehyde erythropoietin on HEK293 kidney cells after silver nanoparticle exposure.

The toxic effects from exposure to silver nanoparticles (AgNPs), which are broadly present in many consumer products, have long raised concerns. Many studies have focused on the mechanisms of nanosilver, which cause toxicity in human cells, but little is known about prevention of this type of injury. This study investigated the in vitro effects of glutaraldehyde erythropoietin (GEPO), a cytoprotective compound derived from erythropoietin, in terms of cell protection against AgNP-induced injury. HEK293 cells were pretreated with or without GEPO before administration of AgNPs. The protective effects of GEPO in this cell line were assessed by the percentage of viable cells, alterations of cell morphology, and the proliferative capability of the cells. In addition, we assessed the role of GEPO in lowering cellular oxidative stress and regulating expression of the anti-apoptotic protein Bcl2. The results showed rescue effects on the percentage of viable and proliferative cells among GEPO pretreated cells. Pretreatment with GEPO maintained the normal cell shape and ultrastructural morphology. Moreover, GEPO reduced the generation of reactive oxygen species in cells and activated expression of Bcl2, which are the major mechanisms in protection against cellular toxicity induced by AgNPs. In conclusion, our study showed that the cytotoxic effects from exposure to AgNPs can be prevented by GEPO.

Anticancer activity of selected Colocasia gigantia fractions.

The objective of this study is to investigate the anticancer potential of the extract of Colocasia gigantea C. gigantea), a plant member of the Araceae family. In the present study, we investigated the cytotoxic activity of C. gigantea extract on cervical cancer (Hela) and human white blood cells (WBC) in vitro. The authors then identified the bioactive ingredients that demonstrated cytotoxicity on tested cells and evaluated those bioactive ingredients using the bioassay-guided fractionation method. The results showed that not all parts of C. gigantea promote cytotoxic activity. The dichloromethane leaf fraction showed significant cell proliferation effect on Hela cells, but not on WBCs. Only the n-hexane tuber fraction (Fr. 1T) exhibited significant cytotoxicity on Hela cells (IC50 = 585 µg/ml) and encouraged WBC cell proliferation. From GC-Mass spectrometry, 4,22-Stigmastadiene-3-one, Diazoprogesterone, 9-Octadecenoic acid (Z)-, hexyl ester and Oleic Acid were the components of Fr 1T that demonstrated cytotoxic potential. In conclusion, C. gigantea's Fr 1T shows potential for cervical cancer treatment.