• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.12
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• pp.1899-1907
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• 2013

We investigated the effects of unripe black raspberry water extract (UBR-W) and oxidation-LDL treatment on cholesterol levels. Experiments using an established human hepatocellular carcinoma cell line (HepG2) showed a time-dependent increase in expression of LDL receptor after UBR-W treatment. Expression of LDL receptor-related genes, such as SREBP1 and 2, increased upon UBR-W treatment. However, expression of HDL-related genes was unaffected by UBR-W. HMG-CoA reductase activity was reduced by UBR-W treatment, whereas HMG-CoA mRNA expression significantly increased. In addition, the ApoB/ApoA1 mRNA level, which is a predictor of cardiovascular risk, was reduced in a time-dependent manner by UBR-W treatment. Macrophage-like cells (RAW 264.7) showed increased expression of ox-LDL-related genes, such as CD36, scavenger receptor-A, adipophilin, and PPAR-gamma, upon ox-LDL treatment compared to untreated control cells, and quantitative lipid analysis indicated a dramatic increase in lipid accumulation. However, UBR-W treatment significantly reduced expression of ox-LDL-related genes and largely prevented lipid accumulation. The results indicate that UBR-W mediates a cholesterol-lowering effect via inhibition of cholesterol synthesis and induction of LDL uptake through SREBP.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3923-3927
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• 2016

Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of $TNF{\alpha}$ gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from $500{\mu}l$ prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples seem to be necessary.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.149-154
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• 2011

Objectives : Myocardial infarction is caused by heart cell death in a region where coronary arteries supplying blood to the region are occluded. In the present study, we determined whether ethanol extract of Cortex fraxini (HY5053) could attenuate heart injury by inhibiting apoptosis. Methods : Improvement of survival of HepG2 cells, a human hepatocellular carcinoma cell line, and reduction of apoptosis under hypoxic conditions (3% $O_2$) were assessed by trypan blue staining and DNA fragmentation assay, respectively. To assess the impact of HY5053 on the heart injury, Sprague-Dawley rats underwent 1 day of the left anterior descending coronary artery occlusion. HY5053 was given by intraperitoneal injection (200 mg/kg) 1 hr prior to the occlusion. Subsequently, the heart were harvested, excised into 4 slices, and the slices were stained with 2,3,5-triphenyl tetrazolium chloride. Finally, the extent of heart injury represented as ischemic index (%) was assessed. Results : Addition of HY5053 (400 ${\mu}g$/mL) into the culture medium for 1 day under ischemic conditions improved the cell survival by 50%, compared with control (0 ${\mu}g$/mL), consequently delayed apoptosis in 6 hr difference. Also, HY5053 (200 mg/kg) reduced the ischemic index by 44%, compared with control (0 mg/kg). Conclusions : These findings suggested that HY5053 attenuated myocardial infarction by inhibiting apoptosis. Thus, Cortex fraxini could be developed as a novel cardioprotectant to complement a currently available treatment, coronary angioplasty.

• Preventive Nutrition and Food Science
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• v.16 no.3
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• pp.217-223
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• 2011

Ischemic stroke constitutes about 80% of all stroke incidences. It is characterized by brain cell death in a region where cerebral arteries supplying blood are occluded. Under these ischemic conditions, apoptosis is responsible for the cell death, at least in part. Goat's-beard (Aruncus dioicus var. kamtschaticus) is a perennial plant that grows naturally in the alpine regions of Korea. In the present study, we first determined whether water extract of goat's-beard (HY1646) and some of its fractions prepared by partitioning with organic solvents could improve the viability of human hepatocellular carcinoma cells (HepG2) cultured under hypoxic condition by blocking apoptotic pathways. Based on the in vitro findings, we subsequently investigated whether HY1646 and the ethyl acetate fraction (EA) selected from cell culture-based screening could attenuate brain injury in a rat middle cerebral artery occlusion (MCAO) model of ischemia (2 hr), followed by 22 hours of reperfusion. The cell number was sustained close to that initially plated in the presence of HY1646 even after 24 hr of cell culture under hypoxic condition (3% $O_2$), at which time the cell number reached almost zero in the absence of HY1646. This improvement in cell viability was attributed to the delay in apoptosis, identified by the formation of DNA ladder in gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA) and butanol, EA was chosen for the animal experiments because EA demonstrated the best cell viability at the lowest concentration (10 ${\mu}g$/mL). HY1646 (200 mg/kg) and EA (10 and 20 mg/kg) significantly reduced infarct size, an index of brain injury, by 16.6, 40.0 and 61.0%, respectively, as assessed by 2,3,5-triphenyl tetrazolium chloride staining. The findings suggest that prophylactic intake of goat's beard might be beneficial for preventing ischemic stroke.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.400-404
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• 1995

Focal nodular hyperplasia is a benign hepatic tumor mainly composed of nodules of hepatocytes and Kupffer cells separated by fibrous septa. In general, it is difficult to differentiate focal nodular hyperplasia and hepatocellular carcinoma on ultrasonography, conventional CT(computerized tomography), and angiography. But IV bolus CT is of particular value in the diagnosis of focal nodular hyperplasia because it can divide enhanced CT into early and late phase and can characterize tumor vascularity and analyze any intratumoral elements. In our case, it was seen as a hypoechoic mass lesion on ultrasonography and hyperdense mass lesion on early-phase IV bolus CT and isodense mass lesion on late-phase IV bolus CT. On angiography, hypertrophy of the feeding artery and tumor staining were well visualized. The patient underwent operation and the mass was pathologically confirmed to a focal nodular hyperplasia. We report the first case of focal nodular hyperplasia on IV bolus CT in Korea.

• Korean Journal of Transplantation
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• v.32 no.4
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• pp.108-112
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• 2018

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.

• Molecules and Cells
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• v.45 no.10
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• pp.702-717
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• 2022

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.432-441
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• 2016

Machaerium cuspidatum, a canopy liana, is a species of genus legume in the Fabaceae family and contributes to the total species richness in the tropical rain forests. In the present study, we investigated the antioxidative and anti-cancer effects of M. cuspidatum and its mode of action. The methanol extract of M. cuspidatum (MEMC) exhibited anti-oxidative activity with an $IC_{50}$ value of $1.66{\mu}g/ml$, and this was attributable to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. MEMC also exhibited a cytotoxic effect and induced morphological changes in a dose-dependent manner in several cancer cell lines including human lung adenocarcinoma A549 cells, human hepatocellular carcinoma HepG2 cells, and human colon carcinoma HT29 cells. Moreover, MEMC treatment induced the accumulation of subG1 population, which is indicative of apoptosis in A549 and HepG2 cells. MEMC-induced apoptosis was confirmed by the increase in Annexin V-positive apoptotic cells and apoptotic bodies using Annexin-V staining and DAPI staining, respectively. Further investigation showed that MEMC-induced apoptosis was associated with the increase in p53 and Bax expression, and the decrease in Bcl-2 expression. In addition, MEMC treatment led to proteolytic activation of caspase-3, 8, and 9 and degradation of poly-ADP ribose polymerase (PARP). Taken together, these results suggest that MEMC may exert a beneficial anti-cancer effect by inducing apoptosis via both the extrinsic and intrinsic pathways in A549 and HepG2 cells.