• Food Science and Biotechnology
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• 제18권1호
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• pp.172-178
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• 2009

Fermented ginseng (FG) is an ethanol extract of ginseng radix processed with $\beta$-galactosidase. It was hypothesized that FG may exert anti-hyperlipidemic and anti-diabetic activities through modulating AMP-activated protein kinase (AMPK) in HepG2 human hepatoma cells. In this study, we showed that AMPK phosphorylation was stimulated by FG. These effects were abolished by pretreatment with an AMPK inhibitor, compound C. In addition, FG regulated the expression of genes associated with lipogenesis and lipolysis, thus causing suppression of hepatic triglyceride accumulation. In vivo study using db/db mice, FG reduced fasting plasma glucose, HbAlc, and insulin resistance index, when compared to diabetic control. FG also increased the phospho-AMPK and glucose transporter 4 (GLUT4) expressions in liver and skeletal muscle, respectively. In liver, expressions of lipogenic gene were decreased whereas expressions of lipolytic genes were induced, when compared to diabetic control. Taken together, we may suggest that FG ameliorates hyperglycemia and hyperlipidemia through activation of AMPK and could be developed as a health functional food or therapeutic agent for type 2 diabetic patients.

• International journal of thyroidology
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• 제11권2호
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• pp.152-159
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• 2018

Background and Objectives: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). Materials and Methods: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. Results: The PTCs with the $BRAF^{V600E}$ mutation and the coexistence of $BRAF^{V600E}$ and TERT promoter mutations showed significantly lower expression of NIS (p<0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p<0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p<0.001) and negative correlations with expressions of genes involved in ERK signaling (r=-0.164, p<0.001) and GLUT-1 gene (r=-0.204, p<0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. Conclusion: The NIS expression was reduced by the $BRAF^{V600E}$ mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.

• Journal of Ginseng Research
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• 제46권1호
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• pp.39-53
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• 2022

Ginsenoside Rb₁ (Rb₁), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb₁ against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb₁ on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb₁ and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb₁ and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb₁ and its clinical applications.

• Molecules and Cells
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• 제44권10호
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• Nuclear Medicine and Molecular Imaging
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• 제41권1호
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• pp.22-29
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• 2007

목적: 방사성옥소를 잘 섭취하는 갑상선 전이암들은 낮은 FDG 섭취를 보이나, 방사선옥소를 섭취하지 않는 경우는 FDG PET에서 잘 보인다고 알려져 있다. 본 연구에서는 원발성 갑상선 유두상암의 FDG 섭취 양상이 어떠한지 알아보고자 하였다. 대상 및 방법: 초음파유도하 세침흡입술로 갑상선 유두상암을 진단을 받고 갑상선 전절제술이 예정되었던 환자 40명들이 시행한 FDG PET/CT들을 대상으로 후향적 분석을 시행하였다. FDG 섭취의 정도는 병변이 주변 조직보다 높은 섭취를 보이는 것을 육안적으로 확인할 수 있는 경우 양성으로 하고 그렇지 않은 경우 음성으로 나누었으며, 병변의 최대 표준화섭취계수(peak SUV)를 구하여 그 크기와 비교하였다. 결과: FDG 섭취 양성소견을 보이는 27례의 갑상선 유두상암들의 평균 크기는 $1.9{\pm}1.4\;cm\;(0.5{\sim}5\;cm)$였고, FDG 섭취를 보이지 않는 13례의 경우는 $0.4{\pm}0.2cm\;(0.2{\sim}0.9\;cm)$이었다. 갑상선의 크기가 1 cm 이상인 19례들은 ($2.5{\pm}1.4\;cm,\;1{\sim}5\;cm$) 모두 FDG 섭취 양성소견을 보였다 (19/19, peak $SUV\;=\;6.4{\pm}5.7,\;1.7{\sim}22.7$). 1cm 미만의 21례의 미세갑상선암들 중 8례가 FDG 섭취 양성소견을 보인 반면 (8/21, peak $SUV\;=\;2.9{\pm}1.3,\;1.7{\sim}5.5$), 13례는 음성소견을 보였다(peak $SUV\;=\;1.2{\pm}0.2,\;1.1{\sim}1.7$). 미세갑상선암들 중 FDG 섭취 양성 소견을 보이는 경우의 크기는 $0.7{\pm}0.1\;cm$으로 음성소견을 보이는 경우의 크기 $0.4{\pm}0.2\;cm$와 비교하여 유의하게 컸다(P=0.01). 결론: 본 보고에서 40례의 원발성 갑상선 유두상암 가운데 1 cm 이상 크기의 갑상선 유두상암들은 모두 FDG 섭취 양성소견을 보였는데, 이는 방사성옥소를 섭취하지 않는 분화도가 나쁜 갑상선암들만 FDG 섭취를 보인다는 이전 문헌의 내용과 상충되며, 이러한 원발성 갑상선 유두상암의 FDG 섭취를 이해하기 위해서는 GLUT 및 NIS 발현과 연관한 후속 연구가 필요하겠다.

• 동의생리병리학회지
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• 제30권1호
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• pp.54-60
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• 2016

Amomum cadamomum Linne (ACL) has long been utilized against the inhibited qi movement related diseases such as dyspepsia, acute gastroenteritis, vomiting and diarrhea in Korean medicine. We speculated that ACL could improve the metabolic disorders such as obesity and type 2 diabetes through removing the phlegm-dampness and promoting the qi movement or stagnation. This study was designed to investigate effects and molecular mechanisms of ACL extract on the improvement of adipocyte dysfunction induced by TNF-α in 3T3-L1 adipocytes. Potential roles of ACL extract in the lipogenesis, inhibition of inflammatory cytokines and insulin resistance, were investigated in this study. Also, we examined the adipose genes and signaling molecules related to insulin resistance and glucose uptake to elucidate its mechanism. Our data demonstrated that TNF-α significantly incresed the release of lipid droplets and the production of MCP-1 and IL-6 from adipocytes. In gene expression, TNF-α reduced the expression of aP2, PPARγ, C/EBPα, GLUT4, and IRS-1 related to lipogenesis and insulin sesitivity, while TNF-α increased the expression of MCP-1 related to inflammation. In addition, TNF-α down-regulated the PPARγ and IRS-1 protein and up-regulated the IRS-1 Ser307 phosphorylation. These alterations induced by TNF-α were prevented by the treatment of ACL extract. Thus, our results indicate that ACL extract can be used to prevent from the TNF-α-induced adipocyte dysfunction through insulin and PPARγ pathways.

• Asian-Australasian Journal of Animal Sciences
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• 제29권8호
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• pp.1095-1101
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• 2016

Ginsenoside Rg1 is a natural compound with various efficacies and functions. It has beneficial effects on aging, diabetes, and immunity, as well as antioxidant and proliferative functions. However, its effect on porcine embryo development remains unknown. We investigated the effect of ginsenoside Rg1 on the in vitro development of preimplantation porcine embryos after parthenogenetic activation in high-oxygen conditions. Ginsenoside treatment did not affect cleavage or blastocyst formation rates, but did increase the total cell number and reduced the rate of apoptosis. In addition, it had no effect on the expression of four apoptosis-related genes (Bcl-2 homologous antagonist/killer, B-cell lymphoma-extra large, Caspase 3, and tumor protein p53) or two metabolism-related genes (mechanistic target of rapamycin, carnitine palmitoyltransferase 1B), but increased the expression of Glucose transporter 1 (GLUT1), indicating that it may increase glucose uptake. In summary, treatment with the appropriate concentration of ginsenoside Rg1 ($20{\mu}g/mL$) can increase glucose uptake, thereby improving the quality of embryos grown in high-oxygen conditions.

• 대한의생명과학회지
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• 제11권3호
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• pp.327-332
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• 2005

Sf21 cells become popular as the host permissive cell line to support the baculovirus AcNPV replication and protein synthesis. The cells grow well on TC-100 medium that contains $0.1\%$ D-glucose as the major carbon source, strongly suggesting the presence of endogenous glucose transporters. However, unlike human glucose transporters, very little is known about the characteristics of the endogenoussugar transporter(s) in Sf21 cells. Thus, some kinetic properties of the sugar transport system were investigated, involving the uptake of 2-deoxy-D-glucose (2dG1c). In order to obtain a true measure of the initial rate of uptake, the uptake of $[^3H]2dGlc$ from both low $(100{\mu}M)$ and high (10 mM) extracellular concentrations was measured over periods ranging from 30 sec to30 min. The data obtained indicated that the uptake was linear for at least 2 min at both concentrations, suggesting that measurements made over a 1min time course would reflect initial rates of the jexpse uptake. To determine $K_m\;and\;V_{max}$ of the endogenous glucose transporter(s) in Sf21 cells, the uptake of 2dG1c was measured over a range of substrate concentrations $(50{\mu}M\~10mM)$ 2dG1c uptake by the Sf21 cells appeared to involve both saturable and non-saturable (or very low affinity) components. A saturable transport system for 2dG1c was relatively high, the $K_m$ value for uptake being < 0.45 mM. The $V_{max}$ value obtained for 2dG1c transport in the Sf21 cells was about 9.7-folds higher than that reported for Chinese hamster ovary cells, which contain a GLUT1 homologue. Thus, it appeared that the transport activity of the Sf21 cells was very high. In addition, the Sf21 glucose transporter was found to have very low affinity for cytochalasin B, a potent inhibitor of human erythrocyte glucose transporter

• 동아시아식생활학회지
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• 제24권3호
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• pp.335-350
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• 2014

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

• Asian-Australasian Journal of Animal Sciences
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• 제24권12호
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• pp.1674-1680
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• 2011

This study was conducted to examine the effects of glucose, chromium picolinate (CrP), and vitamin C (Vit C) on lipid metabolism in Korean native steers fitted with indwelling catheters. A total of 12 Korean native steers were randomly allocated to the following treatments: 1) normal control diet, 2) same as 1) +250 g of glucose by intravenous (IV) infusion, 3) same as 2)+13.5 g CrP administered orally, and 4) same as 3)+2.52 g Vit C by IV infusion. Glucose, Vit C, and CrP treatments were administered for five days. At days 1 and 3, serum insulin was higher in treated animals than in those fed the control diet (p<0.05). Serum non-esterified fatty acid (NEFA) concentration in the steers on treatment 2), control+13.5 g CrP, was lower than those on other treatments at 90 min post-infusion on days 1 and 3 (p<0.05). The expression of peroxisome proliferator-activated receptor-${\gamma}$ (PPAR${\gamma}$)2, stearoyl-CoA desaturase-1 (SCD), fatty acid synthase (FAS), and glucose transporter type 4 (Glut 4) in the longissimus muscle of steers on treatment 2 was higher than those on other treatments. In conclusion, the results suggest that CrP is associated with the regulation of gene expression involved in adipogenesis.