Proceedings of the Korean Society of Toxicology Conference
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2002.11b
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pp.14-40
/
2002
15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.
Jung, Hee Jin;Bang, EunJin;Kim, Byeong Moo;Jeong, Seong Ho;Lee, Gil Han;Chung, Hae Young
Journal of Life Science
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v.29
no.11
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pp.1200-1207
/
2019
Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and $20{\mu}m$. Cell viability assays confirmed that doses of loganin up to $20{\mu}m$ were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with ${\alpha}-MSH$ and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by ${\alpha}-MSH$ and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.
Lee, Yeo Jin;Son, Young Min;Gu, Min Jeong;Song, Ki-Duk;Park, Sung-Moo;Song, Hyo Jin;Kang, Jae Sung;Woo, Jong Soo;Jung, Jee Hyung;Yang, Deok-Chun;Han, Seung Hyun;Yun, Cheol-Heui
Journal of Ginseng Research
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v.39
no.1
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pp.29-37
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2015
Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.
Jung, Yu Jin;Park, Joung Soon;Go, Ji Yun;Lee, Hyo Ju;Kim, Jin Young;Lee, Ye Ji;Nam, Ki Hong;Cho, Yong-Gu;Kang, Kwon Kyoo
Journal of Plant Biotechnology
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v.48
no.3
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pp.124-130
/
2021
Nitrate is an important nutrient and signaling molecule in plants that modulates the expression of many genes and regulates plant growth. In this study, we cover the research status of transcription factors related to the control of gene expression by nitrate signaling in higher plants. Nitrate reductase is a key enzyme in nitrogen assimilation, as it catalyzes the nitrate-to-nitrite reduction process in plants. A variety of factors, including nitrate, light, metabolites, phytohormones, low temperature, and drought, modulate the expression levels of nitrate reductase genes and nitrate reductase activity, which is consistent with the physiological role if. Recently, several transcription factors controlling the expression of nitrate reductase genes have been identified in higher plants. NODULE-INCEPTION-Like Proteins (NLPs) are transcription factors responsible for the nitrate-inducible expression of nitrate reductase genes. Since NLPs also control the nitrate-inducible expression of genes encoding the nitrate transporter, nitrite transporter, and nitrite reductase, the expression levels of nitrate reduction pathway-associated genes are coordinately modulated by NLPs in response to nitrate. Understanding the function of nitrate in plants will be useful to create crops with low nitrogen use.
Ji, Jong-Hun;Kim, Young-Yul;Patel, Kaushal;Cho, Namjoon;Park, Sang-Eun;Ko, Myung-Sup;Park, Suk-Jae;Kim, Jong Ok
Journal of Microbiology and Biotechnology
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v.29
no.2
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pp.297-303
/
2019
Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated $NF-{\kappa}B$ activation is a hallmark of chronic inflammatory diseases and has been responsible for the pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The purpose of this study was to examine the exact effect of dexamethasone on $NF-{\kappa}B$ signaling in rotator cuff tear. We measured $NF-{\kappa}B$ expression in four groups: control, $TNF-{\alpha}$-treated, DEXA-treated, and combined treatment with $TNF-{\alpha}$ and DEXA. Tenocytes were isolated from patients with rotator cuff tears and pre-incubated with $TNF-{\alpha}$ (10 ng/ml), DEXA ($1{\mu}M$), or both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol was analyzed by western blotting and immunofluorescence imaging using confocal microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our study, the combined treatment with DEXA and $TNF-{\alpha}$ showed increased N/C ratios of p65, p50, and p52 compared with those in the $TNF-{\alpha}$ group at all time points. Additionally, in the DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not effective in inhibiting the inflammatory response of $TNF-{\alpha}$-stimulated rotator cuff tear.
Kim, Gun-Hee;Hong, Ka-Kyung;Cho, Han-Baek;Choi, Chang-Min;Kim, Song-Baek
The Journal of Korean Obstetrics and Gynecology
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v.32
no.2
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pp.1-17
/
2019
Objectives: This study was performed to identify the anti-inflammatory effects of Salvia miltiorrhizae radix Water extract (SMW) on lipopolysaccharide (LPS) induced inflammation. Methods: RAW 264.7 cells were treated with 500 ng/ml of LPS. SMW (0.1, 0.25, 0.5 mg/ml) was treated 1 h prior to LPS. Cell viability was measured by MTT assay. Levels of nitric oxide (NO) were measured with Griess reagent and pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B ($NF-{\kappa}B$) activation by western blot. In addition, we observed mice survival rate after LPS and examined their cytokine levels of serum and liver tissue. Results: SMW itself did not have cytotoxic effects in RAW 264.7 cells less than 0.5 mg/ml. SMW treatment inhibited the production of NO, and interleukin $(IL)-1{\beta}$ which is pro-inflammatory cytokine. And SMW treatment inhibited the LPS-induced activation of MAPKs such as extracellular signal-regulated kinase1/2 (ERK1/2), p38 kinases (p38), c-Jun NH2-terminal kinase (JNK) and $NF-{\kappa}B$. In addition, it also showed reducing the level of $IL-1{\beta}$ on the serum and liver tissue of mice. Also, death of LPS-induced mice was inhibited by SMW. Conclusions: The result suggests that treatment of SMW could reduce the LPS-induced inflammation. Thereby, SMW could be used as a protective agent against inflammation. Also, this study could give a clinical basis that SMW could be a drug or agent to prevent inflammatory diseases.
Han, Jang Mi;Gong, So Youn;Sohng, Jae Kyung;Kang, Yue Jai;Jung, Hye Jin
Korean Journal of Food Science and Technology
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v.51
no.2
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pp.141-146
/
2019
Sparassis crispa is an edible mushroom that is distributed in Korea, Japan, Europe, and North America. It exerts various biological activities such as immunopotentiation, anti-diabetic, anti-cancer, and anti-inflammatory effects. Recently, we separated the health functional non-aqueous fraction from the chloroform extract of S. crispa (SCF4). In this study, we evaluated the antiangiogenic activity of SCF4 in human umbilical vein endothelial cells (HUVECs). SCF4 effectively inhibited vascular endothelial growth factor (VEGF)-induced cell growth at concentrations ($5-25{\mu}g/mL$) showing no cytotoxic effects. SCF4 inhibited VEGF-induced invasiveness and tube formation ability, which are in vitro angiogenic features of HUVECs, in a dose-dependent manner. In addition, SCF4 markedly suppressed in vivo angiogenesis of chorioallantoic membrane from growing chick embryos without cytotoxicity. Furthermore, SCF4 downregulated the phosphorylation of VEGFR2, AKT, and ERK1/2, which are major angiogenic signal mediators. These results suggest that SCF4 inhibited angiogenesis by suppressing the VEGFR2 signaling pathways without cytotoxicity.
Lee, Seokhyun;Lee, Ra Ham;Kim, Sung-Jo;Lee, Hak-Kyo;Na, Chong-Sam;Song, Ki-Duk
Asian-Australasian Journal of Animal Sciences
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v.32
no.12
/
pp.1942-1949
/
2019
Objective: Leukocyte cell-derived chemotaxin 2 (LECT2) is associated with several physiological processes including inflammation, tumorigenesis, and natural killer T cell generation. Chicken LECT2 (chLECT2) gene was originally identified as one of the differentially expressed genes in chicken kidney tissue, where the chickens were fed with different calcium doses. In this study, the molecular characteristics and gene expression of chLECT2 were analyzed under the stimulation of toll-like receptor 3 (TLR3) ligand to understand the involvement of chLECT2 expression in chicken metabolic disorders. Methods: Amino acid sequence of LECT2 proteins from various species including fowl, fish, and mammal were retrieved from the Ensembl database and subjected to Insilco analyses. In addition, the time- and dose-dependent expression of chLECT2 was examined in DF-1 cells which were stimulated with polyinosinic:polycytidylic acid (poly [I:C]), a TLR3 ligand. Further, to explore the transcription factors required for the transcription of chLECT2, DF-1 cells were treated with poly (I:C) in the presence or absence of the nuclear factor ${\kappa}B$ ($NF{\kappa}B$) and activated protein 1 (AP-1) inhibitors. Results: The amino acid sequence prediction of chLECT2 protein revealed that along with duck LECT2 (duLECT2), it has unique signal peptide different from other vertebrate orthologs, and only chLECT2 and duLECT2 have an additional 157 and 161 amino acids on their carboxyl terminus, respectively. Phylogenetic analysis suggested that chLECT2 is evolved from a common ancestor along with the actinopterygii hence, more closely related than to the mammals. Our quantitative polymerase chain reaction results showed that, the expression of chLECT2 was up-regulated significantly in DF-1 cells under the stimulation of poly (I:C) (p<0.05). However, in the presence of $NF{\kappa}B$ or AP-1 inhibitors, the expression of chLECT2 is suppressed suggesting that both $NF{\kappa}B$ and AP-1 transcription factors are required for the induction of chLECT2 expression. Conclusion: The present results suggest that chLECT2 gene might be a target gene of TLR3 signaling. For the future, the expression pattern or molecular mechanism of chLECT2 under stimulation of other innate immune receptors shall be studied. The protein function of chLECT2 will be more clearly understood if further investigation about the mechanism of LECT2 in TLR pathways is conducted.
Sleep is an essential factor for living a healthy life, but most modern people complain of poor sleep. For these people, as the need for a means to simply evaluate and manage the quality of sleep increases, devices that can check the sleep state at home without monitoring by an examiner are being developed. The smart sleep mask, which is the subject of this usability test, provides bio-signal monitoring while sleeping so that you can conveniently measure and manage your sleep state for yourself. The purpose of this study is to evaluate the usability and safety of the smart sleep mask, to find and prevent potential factors related to errors in use that may occur, and to develop the comfort and safety of this product. As a result of the formative evaluation of the sleep mask prototype, it was reported that it was difficult to turn on the power and check the results, and that the sleep mask was not comfortable to wear. Different opinions were presented on the size and weight of the sleeping mask by people in different age groups.
Kim, Yoo-Jin;Seo, Kyung Hye;Jang, Gwi Young;Jung, Ji Wook;Kim, Mi Ryeo
The Korea Journal of Herbology
/
v.36
no.3
/
pp.47-53
/
2021
Objectives : Currently, the alopecia is one of the most emotionally stressful syndromes in human life. Human hair dermal papilla cells (HDPCs) play an essential role in controlling hair growth and in regulating hair cycle. We performed MTT assay, cell cycle, and western blot to determine the effects of essential oil from Coicis Semen (ECS) on hair growth in HDPCs. Methods : We monitored cell proliferations by MTT assay in HDPCs. After setting up the safe and effective concentration range to be treated ECS, cell cycle analysis was performed using flow cytometry. Also, the protein expression of hair growth-related factors such as insulin like growth factor-1 (IGF-1), Wnt, extracellular signal-regulated kinase (ERK), serine/threonine-specific protein kinase (Akt) in HDPCs was determined by western blot. Results : As results, cell proliferation was increased in ECS group compared to dimethyl sulfoxide (DMSO) group and minoxidil (MNXD) group. Cell number of ECS group was more decrease in sub G1 phase than cell number of DMSO group. Also, cell number of ECS group increased compared to cell number of DMSO group in G1 phase. Protein expression of ECS group was higher than protein expression of DMSO group on related hair growth factors (IGF-1, Wnt, ERK, Akt). Conclusion : As mentioned above, ECS increased cell proliferation and the protein expression of IGF-1, Wnt, ERK, and Akt. These results suggest that ECS could be used as a potential material for the treatment of alopecia by increasing the proliferation of HDPCs.
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