• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Journal of Marine Life Science
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• v.4 no.1
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• pp.1-13
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• 2019

Fucoidan is a physiologically functional ingredient extracted from seaweed brown algae, which is a sulfated polysaccharide containing fucose as a main molecule backbone. Fucoidan has a variety of immune-modulating or -stimulating effects, including promoting antigen uptake and enhancing anti-bacterial, anti-viral and anti-tumor effects. In addition, recent studies have suggested the possibility of use of fucoidan as a vaccine adjuvant in the field of human vaccine. Use of fucoidan as supplementary feeds have already been studied, but the development of fucoidan as an adjuvant of fish vaccine is still premature. However, the intracellular uptake of fucoidan differs depending on the molecular weight of fucoidan, and there is a limit to the study on specific immune response including the production of antibodies to fish caused by an artificial infection of pathogen. Although the safety of fucoidan has been demonstrated in animal cells, there is a need to confirm the safety of fucoidan in fish. Therefore, active research in this field is needed to use fucoidan as a vaccine adjuvant. This study discussed the effects of fucoidan on immune stimulation, humoraland cellular- immunity including humans and animals. The prospect of fucoidan as a vaccine adjuvant in fisheries also reviewed.

• Korean Journal of Plant Resources
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• v.32 no.3
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• pp.220-227
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• 2019

Stevia rebaudiana (Asteraceae), a perennial plant, has been used as a low-calorie sweetener and is being developed as a therapeutic agent for diabetes, hypertension, myocardial diseases, and microbial infections. Despite the common use of its leaves and stem, the bioavailability of the components present in S. rebaudiana flowers, when used as ingredients of cosmetics, has not been well investigated. Herein, we investigated the antioxidative and antimelanogenic effects of an aqueous extract of S. rebaudiana flowers (Stevia-F). Total flavonoid and phenolic content in Stevia-F were determined to be $8.64{\pm}0.23mg$ of quercetin equivalents/100 g and $631.5{\pm}2.01mg$ of gallic acid equivalents/100 g, respectively. The $IC_{50}$ values of Stevia-F for reducing power, and 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical, hydrogen peroxide, and nitric oxide scavenging activities were 5541.96, 131.39, 466.34, and $10.44{\mu}g/mL$, respectively. Stevia-F showed inhibitory effects on the tyrosinase ($IC_{50}=134.74{\mu}g/mL$) and ${\alpha}$-glucosidase ($IC_{50}=114.81{\mu}g/mL$) activities. No significant cytotoxicity of Stevia-F was observed in B16F10 cells, treated with up to $100{\mu}g/mL$ of the extract for 24 and 48 h (p > 0.05). Stevia-F ($1-100{\mu}g/mL$) suppressed ${\alpha}$-melanocyte stimulating hormone-induced melanin production in B16F10 cells (p < 0.05) and also inhibited the cellular tyrosinase activity (p < 0.05). Overall, our results show that Stevia-F possesses potential for inhibiting tyrosinase and ${\alpha}$-glucosidase activities and has significant antioxidant capacity. The antimelanogenic potential of Stevia-F should extend the usage of S. rebaudiana flowers in the development of skin-whitening products.

• Korean Journal of Environmental Biology
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• v.37 no.1
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• pp.72-81
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• 2019

Bisphenol A (BPA), a representative endocrine disrupting chemicals, has adverse effects on growth, development and reproduction in aquatic organisms. The object of this study was to investigate the modulation of antioxidant enzyme-coding genes using quantitative real time RT-PCR (qRT-PCR), enzyme activity and total protein content, to understand oxidative stress responses after exposure to BPA for 48 h in brackish water flea Diaphanosoma celebensis. The BPA ($3mg\;L^{-1}$) significantly upregulated the expression of Cu/Zn-SOD, Mn-SOD, and catalase (CAT) mRNA. Three GST isoforms (GST-kappa, GST-mu, and GST-theta) mRNA levels significantly increased at the rate of $0.12mg\;L^{-1}$ of BPA. In particular, GST-mu showed the highest expression level, indicating its key role in antioxidant response to BPA. SOD activity was induced with a concentration-dependent manner, and total protein contents was reduced. These findings indicate that BPA can induce oxidative stress in this species, and these antioxidants may be involved in cellular protection against BPA exposure. This study will provide a better understanding of molecular mode of action of BPA toxicity in aquatic organisms.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.31 no.3
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• pp.202-212
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• 2021

Objectives: The reproductive health of female workers has been extensively investigated in South Korea and other countries worldwide. However, few studies have discussed the reproductive health of male workers. In this study, we reviewed the recent literature that reports on the effects of occupational exposure on the reproductive health of male workers and the health of their children. Methods: In May 2020 we used the PubMed search engine to search the literature over the last 10 years and chose case-control, cohort, and cross-sectional studies and reviews. We selected epidemiological studies that investigated the association between pre-pregnant occupational exposure and the reproductive health of male workers and the health of their children. We excluded case reports, non-epidemiological studies (animal experiments, cellular-level experiments, and similar articles), and studies that described postnatal occupational exposure. Results: We eventually selected 23 studies. The studies that included exclusively male workers reported that those employed in the agricultural sector or those exposed to pesticides showed lower blood levels of reproductive hormones and a high risk of lympho-hematopoietic system cancer in their children. Male workers exposed to complex organic solvents and organic compounds showed a high risk of poor semen quality, increased time to pregnancy, decreased blood levels of reproductive hormones, and a high risk of lympho-hematopoietic system cancer in their children. Male workers employed in occupations that involved significant social contact, or in the leather and livestock industries, and in occupations with high levels of exposure to lead and organic solvents showed a high risk of malignancies, including lympho-hematopoietic system cancer, neuroblastoma, and central nervous system tumors in their children. Studies that investigated both male and female workers reported that children of male smelters showed a high risk of premature birth, and children of male workers exposed to metals showed a high risk of hypospadias and cryptorchidism. Children of male welders and workers employed in the glass, ceramic, and tile industries showed a high risk of premature birth. Conclusion: The findings of this study will serve as basic data for further research on male workers' reproductive health and provide a scientific basis for the development of strategies to protect the reproductive health of males employed in high-risk occupations. Moreover, the results of this study may provide guidelines to improve the understanding of and knowledge on male workers' reproductive health.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.2
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• pp.158-164
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• 2021

Hypertriglyceridemia is the main risk factor for atherosclerosis. It is reported that triglyceride (TG) induces macrophage cell death, and is involved in the formation of plaques and development of atherosclerosis. We previously reported that TG-induced cell death of macrophages is mediated via pannexin-1 activation, which increases the extracellular ATP and subsequent increase in potassium efflux, thereby activating the caspase-2/caspase-1/apoptotic caspases, including the caspase-8 pathway. Contrarily, some studies have reported that caspase-8 is an upstream molecule of caspase-1 and caspase-2 in several cellular processes. Therefore, this study was undertaken to investigate whether caspase-8 influences its upstream molecules in TG-stimulated macrophage cell death. We first confirmed that caspase-8 induces caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage in TG-treated macrophages. Next, we determined that the inhibition of caspase-8 results in reduced caspase-1 and -2 activity, which are upstream molecules of caspase-8 in TG-induced cell death of macrophages. We also found that ATP treatment restores the caspase-8 inhibitor-induced caspase-2 activity, thereby implying that caspase-8 affects the upstream molecules responsible for increasing the extracellular ATP levels in TG-induced macrophage cell death. Taken together, these findings indicate that caspase-8 potentiates the TG-induced macrophage cell death by activating its upstream molecules.

• The Journal of the Korea Contents Association
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• v.21 no.2
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• pp.85-99
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• 2021

Graphene, called the "dream material" is drawing attention as a groundbreaking new material that will lead the era of the 4th Industrial Revolution. Graphene has high strength, excellent electrical and thermal conductivity, excellent optical permeability, and excellent gas barrier properties. In this paper, as the South Korean government recently announced Green New Deal and Digital New Deal policy, we analyze graphene technology, which is also attracting attention for its application to Corona 19 biosensor, to understand its national R&D trend and knowledge structure, and to explore the possibility of its application. Firstly, 4,054 cases of national R&D project information for the last 10 years are collected from the National Science & Technology Information Service(NTIS) to analyze the trend of graphene-related R&D. Besides, projects classified as green technology are analyzed concerning the government's Green New Deal policy. Secondly, text mining analysis is conducted by collecting 500 recent graphene-related articles from e-newspapers. According to the analysis, the field with the largest number of projects was found to be high-efficiency secondary battery technology, and the proportion of total research funds was also the highest. It is expected that South Korea will lead the development of graphene technology in the future to become a world leader in diverse industries including electric vehicles, cellular phone batteries, next-generation semiconductors, 5G, and biosensors.

• Development and Reproduction
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• v.25 no.1
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• pp.15-24
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• 2021

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

• Molecules and Cells
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• v.44 no.3
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

• Journal of Bio-Environment Control
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• v.31 no.4
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• pp.311-318
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• 2022

Salicylic acid (SA), a phenolic compound, plays a pivotal role in regulating a wide range of physiological and metabolic processes in plants such as antioxidant cellular defense, photosynthesis, and biotic and abiotic stress responses during the growth and development. We examined the effect of exogenous SA application (100 mg·L^-1) on the growth, yield, photosynthetic characteristics, lipid peroxidation, and antioxidant enzyme activity of chili pepper plants under high temperature and drought stress conditions. SA treatment induced increases of net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr) under the stress condition with the highest level after the third treatment. The contents of malondialdehyde and H₂O₂ were significantly lower in the third treatment of SA compared to the control. The activity of ascorbate peroxidase, catalase, peroxidase and superoxide dismutase, increased in treated plants by up to 247, 318, 55 and 54%, respectively compared to the nontreated control. There was no significant difference in the growth characteristics between SA-treated and nontreated plants, while the SA treatment increased marketable yield (kg/10a) by about 15% compared to the nontreated control. Taken together, these results suggest that foliar application of SA alleviates physiological damages caused by the combination of drought and heat stress, and enhances the photosynthetic capacity and antioxidant enzyme activities, thereby improving tolerance to a combination of water deficit and heat stress in chili pepper plants.