• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.51-57
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• 2009

Quantum Dot (QD) nanoparticles are used in various industrial applications, such as diagnostic, drug delivery, and imaging agents of biomedicine. Although QDs are extensively used in many medical science, several studies have been demonstrated the potential toxicity of nanoparticles. The first objective of this study was to investigate the nanotoxicity of QDs in the HaCaT human keratinocyte cell line by focusing on gene expression pattern. In order to evaluate the effect of QDs on gene expression profile in HaCaT cells, we analyzed the differential genes which related to oxidative stress and antioxidant defense mechanisms by using human cDNA microarray and PCR array. A human cDNA microarray was clone set, which was sorted for a list of genes correlated with cell mechanisms. We tried to confirm results of cDNA microarray by using PCR array, which is pathway-focused gene expression profiling technology using Real-Time PCR. Although we could not find the exactly same genes in both methods, we have screened the effects of QDs on global gene expression profiles in human skin cells. In addition, our results show that QD treatment somehow regulates cellular pathways of oxidative stress and antioxidant defense mechanisms. Therefore, we suggest that this study can enlarge our knowledge of the transcriptional profile and identify new candidate biomarker genes to evaluate the toxicity of nanotoxicology.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4203-4209
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• 2015

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.

• Environmental Analysis Health and Toxicology
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• v.23 no.2
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• pp.101-112
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• 2008

Effects of various concentrations of copper on growth change of blue-greenalgae Anabaena flos-aquae were studied. There was significant differences among cultures treated with various concentrations of copper in growth of algae with parameters of cell numbers, specific growth rate (SGR) and chlorophyll contents. Algal growth and SGR were inhibited on by effect of various concentrations of copper more than without copper (ANOVA, F=34.69 p<0.001, F=114.89, p<0.001). The SGRs of various concentrations of copper in media were higher than without copper on 8 days after copper treated. The mean of chlorophyll contents was 1.978 ${\mu}g{\cdot}mL^{-1}$ and 1.648 ${\mu}g{\cdot}mL^{-1}$, respectively, while those of algae in culture without copper was 3.179 ${\mu}g{\cdot}mL^{-1}$ (ANOVA, F=153.74, p<0.001). The cellular morphology was different between media of which copper treated and without copper. The colony of algae in media which copper treated was shorter than without copper. Effects of various concentrations of copper on growth change of blue-green-algae Anabaena flos-aquae occured variety changes of parameters of cell numbers, specific growth rate (SGR), chlorophyll contents and cellular morphology on growth of algae.

• Journal of Microbiology and Biotechnology
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• v.22 no.2
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• pp.170-175
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• 2012

Clostridium difficile toxin A glucosylates Rho family proteins, resulting in actin filament disaggregation and cell rounding in cultured colonocytes. Given that the cellular toxicity of toxin A is dependent on its receptor binding and subsequent entry into the cell, we herein sought to identify additional colonocyte proteins that might bind to toxin A following its internalization. Our results revealed that toxin A interacted with ERK1 and ERK2 in two human colonocyte cell lines (NCM460 and HT29). A GST-pulldown assay also showed that toxin A can directly bind to ERK1 and ERK2. In NCM460 cells exposed to PMA (an ERK1/2 activator), the phosphorylation of ERK1/2 did not affect the interaction between toxin A and ERK1/2. However, an in vitro kinase assay showed that the direct binding of toxin A to ERK1 or ERK2 inhibited their kinase activities. These results suggest a new molecular mechanism for the cellular toxicity seen in cells exposed to toxin A.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.283-289
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• 2019

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.138-143
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• 2008

We investigated if Chlorella vulgaris (CV) has protective effects on cadmium (Cd) induced liver damage in male Sprague-Dawley (SD) rats. Forty rats, aged 5 weeks old and weighed 90-110g, were divided into a control (with Cd free water), 50 ppm of $CdCl_2$ in drinking water treated groups (Chlorella 0% diet group (Cd/CV0%), Chlorella 5% diet group (Cd/CV5%) or Chlorella 10% diet group (Cd/CV10%). All the rats had freely access to water and diet for 8 weeks. The results show that body weight gain and relative liver weight had significantly lower in Cd/CV0%-treated group than in Cd/CV-treated groups. Hepatic Cd contents showed significantly less by feeding CV (P<0.05). Cd/CV0%-treated rats had significantly (P<0.05) higher hepatic T-MTs, and Cd-MTs concentrations, compared to Cd/CV5% or Cd/CV10% treated rats. The MT I/II mRNA was expressed in the liver of all experimental rats. Its expression was more increased in Cd/CV5%- or Cd/CV10%-treated rats, compared to control and Cd-treated rats. Thus, this study suggested that CV would have a protective effect on Cd-treated liver injury by the reduction of Cd concentrations and stimulation of Cd-MT binds in the liver. However, more studies are needed to identify the proper mechanism of CV and liver toxicity.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.100-105
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• 2008

Biochips are a powerful emerging technology for biomedical, environmental applications. Especially, making use of bioseonors in the evaluation of toxicity becomes increasingly important. For biosensor as a toxicity detection, biomolecules like antibodies or aptamers have been developed to specifically capture the toxic target molecules. In addition, the development of optimal chip materials capable of maintaining the activity of embedded biomolecules such as proteins or aptamers has proven challenging. Here, using sol-gel materials, new chip material, whose ability for immobilizing the embedded aptamers and maintaining the ability of embedded aptamers is optimal, was searched. We used sol-gel formulation screening methods previously developed and found the best formulation which shows high sensitive and specific interactions of aptamers. This study results will support the technological advancement for diagnosis and environmental sensor.

• Journal of Preventive Medicine and Public Health
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• v.47 no.2
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• pp.74-83
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• 2014

Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

• Molecules and Cells
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• v.43 no.6
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• pp.530-538
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• 2020

The Gustatory system enables animals to detect toxic bitter chemicals, which is critical for insects to survive food induced toxicity. Cucurbitacin is widely present in plants such as cucumber and gourds that acts as an anti-herbivore chemical and an insecticide. Cucurbitacin has a harmful effect on insect larvae as well. Although various beneficial effects of cucurbitacin such as alleviating hyperglycemia have also been documented, it is not clear what kinds of molecular sensors are required to detect cucurbitacin in nature. Cucurbitacin B, a major bitter component of bitter melon, was applied to induce action potentials from sensilla of a mouth part of the fly, labellum. Here we identify that only Gr33a is required for activating bitter-sensing gustatory receptor neurons by cucurbitacin B among available 26 Grs, 23 Irs, 11 Trp mutants, and 26 Gr-RNAi lines. We further investigated the difference between control and Gr33a mutant by analyzing binary food choice assay. We also measured toxic effect of Cucurbitacin B over 0.01 mM range. Our findings uncover the molecular sensor of cucurbitacin B in Drosophila melanogaster. We propose that the discarded shell of Cucurbitaceae can be developed to make a new insecticide.

• Molecules and Cells
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• v.44 no.8
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• pp.613-622
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• 2021

In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity.