• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.659-667
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• 2017

The present study was designed to evaluate the antioxidant activity and radioprotective effects of Naringin and Naringenin in ${\gamma}$-irradiated mice. The antioxidant activity of Naringin and Naringenin was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Healthy female BALB/c mice were administered Naringin and Naringenin orally ($90{\mu}M/dose$ and $180{\mu}M/dose$) for 7 consecutive days prior to ${\gamma}$-irradiation (6 Gy). Naringenin displayed a much higher antioxidant activity in ABTS and FRAP than naringin. ${\gamma}$-irradiation resulted in cellular damage with decreased spleen and thymus indices and white blood cells (WBC) count. Additionally, ${\gamma}$-irradiation significantly increased lipid peroxidation and decreased the levels of antioxidant enzymes and glutathione (GSH) in the liver tissue. Strikingly, prior administration of Naringenin resulted in considerable prevention of these symptoms. Protection against ${\gamma}$-irradiation-induced cellular damage by Naringenin is likely due to its higher its antioxidant activity. Together, these results confirm that Naringenin is a potent antioxidant and radioprotector.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4077-4082
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• 2016

Background: Hepatocellular carcinoma (HCC) is a dreadful complication of end stage liver disease with high morbidity and mortality. Aim: The aim was to assess the role of serum talin-1 and non-invasive fibrosis in patients with HCC. Materials and Methods: A total of eighty seven subjects were enrolled, with 22 two healthy individuals as a control group (n=22), 22 patients in the cirrhosis group and finally 43 in the group with HCC diagnosed with positive triphasic CT abdomen criteria. Serum talin-1 and noninvasive fibrosis parameters were assessed in all subjects. Results: Compared to the cirrhosis group, patients with HCC had higher serum talin-1 ($32.9{\pm}12.6$ vs. $11.1{\pm}2.79ng/ml$), FIB4 ($9.96{\pm}15.3$ vs. $2.90{\pm}1.87$) and $fibro-{\alpha}$ ($10.9{\pm}18.1$ vs. $1.55{\pm}0.28$) but not fibrosis index scores ($4.47{\pm}0.95$ vs. $4.98{\pm}0.96$; p=0.046). Patients with large focal lesions (${\geq}5cm$) had different ALBI scores ($-1.02{\pm}0.63$ vs. $-1.72{\pm}0.59$; p=0.001) serum talin-1 ($9.72{\pm}13.81$ vs. $28.6{\pm}38.89ng/ml$; p=0.007) and fibrosis index scores ($0.85{\pm}0.99$ vs. $4.20{\pm}4.85$; p=0.026). No statistical differences were noted between patients with and without portal vein thrombosis. For detection of HCC, serum talin-1 had 97.7% sensitivity and 100% specificity with a 17.2 ng/ml cutoff. AFP at a 13.7 ng/ml cutoff had 72.1% sensitivity and 6.3.6% specificity. The cutoff for the $fibro-{\alpha}$ score was 1.61 with 81.4% sensitivity and 77.3% specificity. Serum talin-1 (odds=1.08; C.I=1.016-1.150; p=0.014), fibrosis index score (odds=2.35; C.I=1.055-5.217; p=0.037) and the ALBI score (odds=6.9; C.I=1.924-24.708; p=0.003) were predictors of large focal lesions. Conclusions: Serum talin-1, AST/ALT ratio, $fibro-{\alpha}$ score are useful for the assessment of HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1367-1370
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• 2015

Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ${\leq}2mg/dL$ (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was $6.05{\mu}mol/L$ with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

• Analytical Science and Technology
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• v.21 no.5
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• pp.383-391
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• 2008

International Agency for Research on Cancer (IARC) has classified it as a possible carcinogen and World Health Organization (WHO) has suggested 50 ng/mL as a guideline value for 1,4-dioxane. Considering the toxicity of 1,4-dioxane and ingestion rate of drinking water, the monitoring of 1,4-dioxane in drinking water in Nakdong river is very important. We analyzed 1,4-dioxane four times per year for the 12 samples of treated water and 4 samples of raw water in Nakdong river in Korea from 2000 to 2007 and surveyed the trend of concentrations of 1,4-dioxane. As a results of analysis, 1,4-dioxane was detected from 0.24 to 240.2 ng/mL in treated water and from 0.39 to 81.9 ng/mL in raw water from 2000 to 2007. The average concentrations are 22.68 ng/mL and 19.15 ng/mL in treated water and raw water, respectively. The detected concentrations was decreased but frequency of detection was not changed since establishment of regulation in 2004. Results of comparison of 95 percentile excessive cancer risk of 1,4-dioxane in treated and raw water were each $6.63{\times}10^{-6}$, $3.17{\times}10^{-6}$ before 2004 and $2.10{\times}10^{-6}$, $1.22{\times}10^{-6}$ after 2004. Also, comparing the detected concentration and frequency for each season, these were more detected the concentration and frequency for 1,4-dioxane in treated and raw water from winter to spring.

• 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.

• Journal of Haehwa Medicine
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• v.24 no.2
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• pp.35-57
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• 2016

Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.

• Journal of Pharmacopuncture
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• v.12 no.4
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• pp.63-76
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• 2009

This study was performed to observe the effect of Keughachukeo-tang(KH) extract on the hepatocellular carcinogenesis and acute liver damage induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into four; normal group(Nor), acute liver damage and hepatocellular cancer inducing control group(Con), KH extract 350㎎/㎏/day(KHA), and 700㎎/㎏/day(KHB) administered groups to Con. The results obtained are as follows: The body weight increased in KHA and KHB than Con from 7th week to the 8th week. The activities of Alanine aminotransferase(ALT) were the most increased in the Con among experimental group. The activities of aspartate aminotransferase(AST), alkaline phosphatase(ALP), and lactacte dehydrogenase(LDH) were significantly decreased(p$<$0.05) in the KHA and KHB compared with Con. Alpha fetoprotein(AFP) were the most increased in the Con among experimental groups. The activities of superoxide dismutase(SOD) were the most increased in the Con among experimental groups. The activities of catalase were significantly increased(p$<$0.05) in the KHA and KHB compared with Con. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and KH extract administerd groups. The number of hepatic p53 positive cells was reduced in the KH extract administered groups compared with Con. These results suggest that administration of KH extract suppress or retard on the Hepatocellular Carcinogenesis and acute liver damage induced by DENA and $CCl_4$ in Rats.

• Analytical Science and Technology
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• v.24 no.2
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• pp.135-141
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• 2011

MMPs (Matrix metalloproteinases) are enzymes playing an important role to turnover and remodel main protein compositions of extracellular matrix. MMP-2 and MMP-9 of MMPs having a catalytic domain which is apart from a hemopexin-like domain part, are different from the other MMPs pertaining fibronectinlike domain close to hemopexin-like domain. It was reported that the development of MMP-9 restrainer can prevent the transfer of liver cancer. In this study, MMP-9 restrainers were extracted and purified from Hovenia dulcis Thunberg. The each fractionary part was examined to investigate the inhibitory effect on MMPs. Three compounds, compound A and B eluted with ethyl acetate (EA) and compound C with methanol, were identified by $^1H$ and $^{13}C$ NMR, GC/MS, and FT-IR. Compound A is considered as a kind of catechine type compound having a benzene ring substituted by hydroxyl and methoxyl groups. Compound B and C are nobiletin type compound pertaining a carbonyl group. Compound A, B and C showed 76%, 66% and 71% of inhibition effect on MMP-9 at 1.0% concentration, respectively. Compound A showed the best inhibition effect on MMP-9.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.129-136
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• 2015

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.5-24
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• 2009

Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.