• Molecules and Cells
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• v.39 no.6
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• pp.508-513
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• 2016

To investigate the potential therapeutic effects of polyphenols in treating Pb induced renal dysfunction and intoxication and to explore the detailed underlying mechanisms. Wistar rats were divided into four groups: control groups (CT), Pb exposure groups (Pb), Pb plus Polyphenols groups (Pb+PP) and Polyphenols groups (PP). Animals were kept for 60 days and sacrificed for tests of urea, serum blood urea nitrogen (BUN) and creatinine. Histological evaluations were then performed. In vitro studies were performed using primary kidney mesangial cells to reveal detailed mechanisms. Cell counting kit-8 (CCK-8) was used to evaluate cell viability. Pb induced cell apoptosis was measured by flow cytometry. Reactive oxygen species (ROS) generation and scavenging were tested by DCFH-DA. Expression level of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1-${\beta}$ (IL-1-${\beta}$) and IL-6 were assayed by ELISA. Western blot and qPCR were used to measure the expression of ERK1/2, JNK1/2 and p38. Polyphenols have obvious protective effects on Pb induced renal dysfunction and intoxication both in vivo and in vitro. Polyphenols reduced Pb concentration and accumulation in kidney. Polyphenols also protected kidney mesangial cells from Pb induced apoptosis. Polyphenols scavenged Pb induced ROS generation and suppressed ROS-mediated ERK/JNK/p38 pathway. Downstream pro-inflammatory cytokines were inhibited in consistency. Polyphenol is protective in Pb induced renal intoxication and inflammatory responses. The underlying mechanisms lie on the antioxidant activity and ROS scavenging activity of polyphenols.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.570-576
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• 2019

Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with ${\alpha}$-naphthoflavone (${\alpha}-NF$), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with ${\alpha}-NF$ or used an siRNA against AhR. Expression of LC3-II induced by PM was decreased in a dose dependent manner by ${\alpha}-NF$. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-II and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.

• Animal cells and systems
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• v.16 no.3
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• pp.190-197
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• 2012

Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

• Journal of Environmental Analysis, Health and Toxicology
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• v.21 no.4
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• pp.243-251
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• 2018

Pharmaceuticals in wastewater effluents have been recognized as emerging pollutants threatening freshwater organisms. To extend understanding for bioaccumulation and toxicity in those organisms, information on biotransformation products (or metabolites) and their metabolic pathway are crucial. The aim of the present study is to identify and elucidate metabolites of pharmaceuticals formed in exposed organisms using suspect and nontarget screening approach using LC-HRMS. As the target pharmaceuticals, carbamazepine, ketoprofen, metoprolol, propranolol, and verapamil were selected whereas Daphnia magna and Gammarus pulex were used as test organisms. After 24h exposure, metabolites formed in the organisms were identified using LC-HRMS. The structures of metabolites were elucidated via analysis of MS/MS fragment pattern and the comparison with fragment database. As the results, a total of 10 metabolites were identified for 5 parent compounds (C253/C356 for carbamazepine, K211 for ketoprofen, M256 for metoprolol, P218/P276/P306 for propranolol, V196/V291/V441 for verapamil). Among them, the presence of C253 and V291 was confirmed using standard materials. Most of the identified metabolites were formed through oxidative reactions such as hydroxylation, N-demethylation, and dealkylation. Cysteine conjugation (phase II reaction) metabolite (C356) for carbamazepine was found in daphnia. The metabolic pathway of verapamil showed similar metabolic pathways and metabolic pathways for both species. Although the toxicological information on the identified metabolites could not be confirmed, the molecular structure information of the proposed metabolites can be used for future evaluation and prediction of toxicity.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1615-1623
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• 2021

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.242-248
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• 2016

Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.

• Journal of Life Science
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• v.31 no.4
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• pp.442-451
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• 2021

Microplastics are fragments of any type of plastic with a size less than 5 mm. Ocean pollution by microplastics is now a worldwide concern in relation to marine ecosystems and human health. The widespread contamination by microplastics means that they can be ingested by and accumulated in diverse species of wildlife, such as fish, mussels, oysters, clams, and scallops. Once ingested, the microplastics can be observed in the intestines, liver, and kidney, and even in the brain. Seafood is one of the major sources of protein intake in humans; therefore, seafood consumption could be pathway for human microplastics exposure. Accumulating evidence indicates that repeated oral exposure to microplastics induces pathologic and functional changes in the reproductive, cardiac, gastrointestinal, endocrine, and even nervous systems of rodents. Maternal exposure to microplastics during gestation and lactation alters metabolic homeostasis in the offspring. Given that seafood provides more than 20% of the total protein intake by over 310 million people worldwide, a reasonable assumption is that microplastics could be substantially accumulated in the human body and impair physiological function. In this review, we have summarized the current status of microplastics contamination in the ocean, their accumulation and toxicities in marine animals and rodents, their exposure to humans, and their potential impacts on human health.

• Journal of Environmental Science International
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• v.14 no.12
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• pp.1093-1102
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• 2005

Effects of abscisic acid(ABA) and temperature on the anthocyanin accumulation and phenylalanine ammonia Iyase(PAL) activity were investigated in seedlings of Arabidopsis thaliana. In time course study, exogenous application of ABA $(50-1000\;{\mu}M)$ led to a noticeable increase in anthocyanin pigments which persisted over the following 5 days. Anthocyanins increased in concert with the chlorophyll loss. The activity of PAL, a key enzyme in the phenylpropanoid pathway, increased on exposure to ABA and reached maximum on the 4th day, This result shows that anthocyanin synthesis and PAL activity have a close physiological relationships. In the effects of temperatures ($10^{\circ}C,\;17^{\circ}C,\;25^{\circ}C$and $30^{\circ}C$) on anthocyanin accumulation and PAL activity in seedlings, a moderate-low temperatures ($17^{\circ}C$) enhanced both anthocyanin content and PAL activity, whereas elevated temperatures ($30^{\circ}C$) showed low levels of anthocyanin and PAL activity, suggesting a correlation between temperature-induced anthocyanin synthesis and the accumulation of PAL mRNA. Simultaneous application of ABA with temperatures Induced higher anthocyanin synthesis and PAL activity in seedlings than ABA or temperature stress alone. Moderate-low temperature with ABA exposure elicited the maximal induction of anthocyanin synthesis and PAL activity. Therefore, ABA treatment significantly increased thermotolerance in .A. thalinan seedlings. Ethephon and ABA showed similar mode of action in physiological effects on anthocyanin accumulation and PAL activity. Our data support that anthocyanins may be protective in preventing damage caused by environmental stresses and play an important role in the acquisition of freezing tolerance.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.4 no.3
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• pp.223-229
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• 2003

Annual radiation dose of residential individuals near 4 nuclear power plants in Korea was calculated via K-DOSE 60 based on the updated ICRP-60. The critical exposure variables were chosen as radionuclides, exposed organs and intake pathways. From the calculation results, the critical nuclides were found to be $^3$H, $^{133}$ Xe, $^{60}$ Co for Kori plants and $^{14}$ C, $^{41}$ Ar for Wolsung plants. The most critical pathway was 'vegetable intake' for adults and 'milk intake' for infants. However, there was no preference in the effective organs. Sensitivity analyses showed that the chemical composition in a nuclide much more influenced upon the radiation dose than any other input parameters such as food intake, radiation discharge, and transfer/concentration coefficients by more than 10$^2$ factor. The effect of transfer/concentration coefficients on the radiation dose was negligible. All input parameters showed highly estimated correlation with the radiation dose, approxinated to 1.0.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.11
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• pp.1639-1645
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• 2002

The purpose of this study was to investigate the effects of aflatoxin $B_1$ ($AFB_1$) on the ultracellular morphology alteration, apoptosis induction and reactive nitrogen and oxygen intermediates production of peritoneal macrophages (DPM) from mule ducks. The ducklings were purchased from a commercial hatchery, and were fed a corn-soybean based diet. As the ducklings were grown up to 3 wk of age, the Sephadex-elicited peritoneal exudative cells (PEC) were used as the source for duck peritoneal macrophages. The ultracellular morphology study showed that significant number of cells shifted from category I (normal cell with ruffled membrane) and II (cell membrane blebbing) to category III (cell membrane blebbing and even rupture) after DPM were incubated with $AFB_1$ ($20{\mu}g/ml$) for 12 to 48 h. When DPM were exposed to $AFB_1$ in vitro, the production of NO, $H_2O_2$ and $O_2{^-}$ in macrophages was reduced after 12-48 h incubation with previous LPS stimulation. There was a DNA laddering pattern observed in DPM incubated with $AFB_1$ 5, 10, 20, 50 or $100{\mu}g/ml$ for 12 h. Evidence also revealed that the percentage of apoptotic cells was increased along with the elevation of $AFB_1$ concentration. The results suggest that $AFB_1$ exposure causes duck macrophages going on apoptotic pathway through evidence of ultracellular morphology alteration and DNA laddering in agarose electrophoresis. The production of reactive nitrogen and oxygen intermediates of duck macrophages also depressed after $AFB_1$ exposure, and this implied that $AFB_1$ could cause deteriorated functions of bacteriocidal and tumoricidal activity in duck macrophages.