• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.4
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• pp.731-738
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• 1998

The present study was aimed to investigate the effect of dietary supplementation of $\beta$-carotene on vitamin A metabolism in ethanol-fed rats. Sprague-Dawley rats weighing 190~210g were fed a liquid diet containing 36% of total calories as ethanol for 6 weeks. The pair-fed control rats(1BP group, 2BP group) were given an isocaloric amount of diet containing sucrose instead of ethanol on the following day. Additionally, the liquid diet, contained different levels of $\beta$-carotene(1BE group: 2.1, 2BE group: 21mg/L liquid diet). Body weight gains and food efficiency ratios of ethanol groups were lower than those of pair-fed groups. This effect did not change with dietary supplementation of $\beta$-carotene. The levels of plasma and hepatic retionl were decreased after chronic ethanol feeding, but the values in 2BE group were higher than in 1BE group. The content of hepatic retinoic acid tended to increase in proportion to $\beta$-carotene supplementation. There results suggest that ethanol consumption may affect the vatamin A methabolism and reduce the conversion of $\beta$-carotene to retinol in rats.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Preventive Nutrition and Food Science
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• v.3 no.1
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• pp.56-61
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• 1998

This study was conducted to investigate the effect of dietary supplementation of vitamin A on the membrane property and ultrastructure in ethanol-administered rat livers. Male Sprague-Dawley rats weighing of 130 ~150g were fed with experimental diets for 7 weeks. The diets contained different types of vitamin A which were $\beta$-carotene, retinyl acetate and retinoic acid. After feeding theexperimental diets for 7 weeks, a dose of 3.0g ethanol (30%, W/V)/kg B.W was injected to rats intraperitoneally. Control rats received 0.9% saline containing isocaloric sucrose instead of ethanol. Plasma membrane fluidity of liver decreased in rats fed with vitamin a -Deficient diet with ethanol as compared to that of control rats. Fluidity change of liver plasma membrane that ethanol had induced was influenced by dietary supplementation of vitamin A, but not influenced by the type of supplemented vitamin. A . The ultrastructural changed of hepatic mitrochondria were observed in some rats such as vitamin A-deficient rats with ethanol. Inadequate consumptionof vitamin A contributed to ultrastructural changes such as swelled mitochondria occurred by ethanol-induced hepatotoxicity. Although accurate mechanism involved in the plasma membrane-stabilizing effect of vitamin A is still unclear, dietary supplementation of vitamin A such as retinyl acetate is neede to modulate this change. The direct involvement of membrane property on the cell damage caused by ethanol treatment remains to be established.

• Molecules and Cells
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• v.42 no.10
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• pp.721-728
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• 2019

Non-structural protein 1 (NS1) of influenza virus has been shown to inhibit the innate immune response by blocking the induction of interferon (IFN). In this study, we isolated two single-stranded RNA aptamers specific to NS1 with $K_d$ values of $1.62{\pm}0.30nM$ and $1.97{\pm}0.27nM$, respectively, using a systematic evolution of ligand by exponential enrichment (SELEX) procedure. The selected aptamers were able to inhibit the interaction of NS1 with tripartite motif-containing protein 25 (TRIM25), and suppression of NS1 enabled retinoic acid inducible gene I (RIG-I) to be ubiquitinated regularly by TRIM25. Additional luciferase reporter assay and quantitative real-time PCR (RT-PCR) experiments demonstrated that suppression of NS1 by the selected aptamers induced IFN production. It is noted that viral replication was also inhibited through IFN induction in the presence of the selected aptamers. These results suggest that the isolated aptamers are strongly expected to be new therapeutic agents against influenza infection.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.226-232
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• 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.

• BMB Reports
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• v.56 no.5
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• pp.296-301
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• 2023

Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocyte-specific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.104-104
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• 2003

As an effort to direct differentiation of human embryonic stem (hES, MB03) cells to dopamine-producing neuronal cells, Nurr1 was transfected using conventional transfection protocol into MB03 and examined the expression of tyrosine hydroylase (TH) after differentiation induced by retinoic acid (RA) and ascorbic acid (AA). Experimentally, cells were transfected with linearized Nurr1 cDNA in pcDNA3.1 (+)-hygovernight followed by selection in medium containing hygromycin-B (150 $\mu$/ml). Expression of Nurr1 mRNA was confirmed by RT-PCR and protein by immunocytochemistry in the drug resistant clones. In order to study the effect of Nurr1 protein on the differentiation pattern of ES cells, one of the positive clones (MBNr24) was allowed to form embryoid body (EB) for 2 days and were induced to differentiate for another 4 days using RA (1 $\mu M$) and AA (50 mM) (2-/4+ protocol) followed by selection in N2 medium for 10 or 20 days. After 10 days in N2 medium, cells immunoreactive to anti-GFAP, anti-TH, or anti-NF200 antibodies were 38.8%, 11%, and 20.5%, respectively. After 20 days in N2 medium, cells expressing GFAP, TH, or NF200 were 28%, 15% and 44.8%, respectively but approximately 9% of MB03 expressed TH protein when the cells were induced to differentiate using a similar prorocol, These results suggest that ectopic expression of Nurr1 enhances generation of TH+ cells as well as neuronal cells when hES cells were differentiated by 2-/4+ protocol.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.103-103
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• 2003

The purpose of this study is to evaluate an efficacy of in vitro differentiated human embryonic stem (hES, MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models MB03 was genetically modified to express Nurr1 protein and was induced to differentiate according to 2-/4+ protocol using retinoic acid and ascorbic acid. The differentiation-induced cells were selected for 10 to 20 days thereafter in N2 medium. Upon selection, cells expressing GFAP, TH, or NF200 were 38.8%, 11%, and 20.5%, respectively. in order to examine therapeutic effects of the differentiated cells in PD animal model, rats were unilaterally lesioned by administration of 6-kydroxydopamine HCI (6-OHDA) into medial forebrain region (MFB, AP -4.4 mm, ML 1.2 mm, DV 78 mm with incision bar set at -2.4 mm), as a reference to bregma and the surface of the skull. Confirmation of successful lesion by apomorphine-induced rotational behavior, differentiated cells were transplanted into the striatum (AP 1.0, ML 3.5, DV -5.0; AP 0.6, ML 2.5, DV -4.5). Improvements of asymmetric motor behavior by the transplantation were examined every two weeks after the surgery. In two weeks, numbers of rotation by the experimental rats were $-14.8 \pm 33.9%$ (P<0.05) of the number before transplantation, however, the ratio increased slightly to $13.6 \pm 56.3%$ in six weeks. In contrast, the ratio of sham-grafted animals ranged from 112.3+8.5% to 139.2+28.9% during the examination. Immunohistochemical studies further confirmed the presence, survival, migration, and expression of TH of the transplanted human cells.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.79-79
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• 2003

Embryonic stem cells are capable of differentiating into a variety of cell lineages. However, the ultimate results of differentiation in vitro greatly depend on the duration of treatment and kinds of differentiating inducers added. In order to investigate the efficiencies of various differentiation inducers and the methods of treatment, we examined differentiation patterns of human embryonic stem cell (hESC, MB03) according to several different protocols. Exp. I) Upon differentiation using retinoic acid and ascorbic acid (RA/AA), embryoid bodies (EB, for 4days) derived from hESC was exposed to Rh (10$^{-6}$ M) and AA (50 mM) for 4 days, and were allowed to differentiate in N2 medium for 7, 14, 21, or 28 days. Exp. II) When bFGF was used, neuronal precursor cells were selected for 8 days in N2 medium after EB formation. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14, 21 or 28 days. Exp. III) In addition, to examine the effects of neurotrophic factors in the production of mature neurons, groups of cells were exposed to either BDNF (5 ng/ml) or TGF-$\alpha$(10 ng/ml) during the 28 days of final differentiation. Differentiation patterns of RA/AA or bFGF treated groups were very similar; approximately 82% and 83% of the cells, respectively, were positive for anti-NF200 antibody, while it was about 10% and 11%, respectively, for anti-NF160 antibody in 28 days in N2 medium. Alsor, cells expressing TH were as low as 5%, while the cells doubled when matured at the presence of either BDNF or TGF-$\alpha$. Cells immunoreactive to anti-GAD antibody were approximately 20%. These results suggest that a maturation step rather than differentiation induction step, which is formation of EB, effects more decisively to the ultimate differentiation pattern.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1554-1562
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• 2018

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.