• Title/Summary/Keyword: Human liver

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Effects of persimmon leaf extracts on proteasome activity in HepG2 human liver cancer cells (감잎 추출물이 HepG2 인간 간암 세포의 proteasome 활성에 미치는 영향)

  • Kim, Soyoung;Yoon, Hyungeun
    • Korean Journal of Food Science and Technology
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    • v.51 no.4
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    • pp.393-397
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    • 2019
  • Proteasome inhibitors can promote apoptosis and cell cycle arrest in cancer cells by inhibition of nuclear factorkappaB ($NF-{\kappa}B$) activation. The purpose of this study was to investigate the effects of persimmon leaf extract (PSE) on proteasome activity in HepG2 human liver cancer cells. PSE treatment inhibited the proteasome activity and $NF-{\kappa}B$ activation in a dose-dependent manner in HepG2 human liver cancer cells (p<0.05). PSE treatment increased the population of cells in G2/M and sub-G1 phases. The results suggested that PSE is one of the candidate substances that may be developed into a proteasome inhibitor.

Inhibitory Potential of Bilobetin Against CYP2J2 Activities in Human Liver Microsomes

  • Wu, Zhexue;Jang, Su-Nyeong;Park, So-Young;Phuc, Nguyen Minh;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.11 no.4
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    • pp.113-117
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    • 2020
  • Cytochrome P450 2J2 (CYP2J2) is a member of the cytochrome P450 superfamily, and is known to be arachidonic acid epoxygenase that mediates the formation of four bioactive regioisomers of epoxyeicosatrienoic acids (EETs). CYP2J2 is also involved in the metabolism of drugs such as albendazole, astemizole, danazol, ebastine, and terfenadine. CYP2J2 is highly expressed in the heart and cancer tissues. In this study, the inhibitory potential of ten natural products against CYP2J2 activity was evaluated using human liver microsomes and tandem mass spectrometry. Among them, bilobetin, which is a kind of biflavonoid, exhibits a strong inhibitory effect against the CYP2J2-mediated astemizole O-demethylation (IC50 = 0.73 μM) and terfenadine hydroxylation (IC50 = 0.89 μM). This result suggests that bilobetin can be used as strong CYP2J2 inhibitor in drug metabolism study.

In Vitro Metabolism of a New Cardioprotective Agent, KR-33028 in the Human Liver Microsomes and Cryopreserved Human Hepatocytes

  • Kim Hyojin;Yoon Yune-Jung;Kim Hyunmi;Cha Eun-Young;Lee Hye Suk;Kim Jeong-Han;Yi Kyu Yang;Lee Sunkyung;Cheon Hyae Gyeong;Yoo Sung-Eun;Lee Sang-Seop;Shin Jae-Gook;Liu Kwang-Hyeon
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1287-1292
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    • 2005
  • KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.

The Effects of Jehasuogamibang on Antioxidation Activity and Dietary Hyperlipidemia-induced Mice (제하수오가미방(製何首烏加味方)이 고지혈증 및 산화적 손상에 미치는 영향)

  • Youn, Hyeon-Deok;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Seol, In-Chan;Kim, Yoon-Sik
    • The Journal of Internal Korean Medicine
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    • v.35 no.3
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    • pp.244-261
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    • 2014
  • Objectives: This experiments were performed to determine the effects of the Jehasuogamibang (製何首烏加味方: JHGB) on antioxidationactivity and hyperlipidemia induced by a hypercholesterolemic diet in mice. Methods: After treatment with JHGB expert safety in cytotoxicity and toxicity of Human fibroblast cells and liver and kidney, effect on Reactive Oxygen Species, serum total cholesterol, LDL-cholesterol, triglyceride, glucose, HDL-cholesterol, lipid peroxid of liver tissue, significantly increased SOD and catalase. Results: 1. JHGB showed safety in cytotoxicity and toxicity of human fibroblast cells and liver and kidney. 2. JHGB showed significant inhibitory effect on reactive oxygen species. 3. JHGB significantly decreased serum total cholesterol, LDL-cholesterol, triglyceride, and glucose, and significantly increased serum HDL-cholesterol. 4. JHGB significantly decreased lipid peroxide of liver tissue and significantly increased SOD and catalase. Conclusions: These results suggest that Jehasuogamibang is effective in antioxidationactivity and dietary hyperlipidemia-induced mice.

Amebic liver abscesses resulting in diagnosis of human immunodeficiency virus infection (아메바 간농양으로 진단에 이른 인간 면역 결핍증)

  • Kim, Seok Weon;Kwon, Hyeok Choon;Nam, Seung Woo;Choi, Jong Kyung;Chung, Joo Won;Jang, Dong Won;Park, Soo Yoen
    • Journal of Yeungnam Medical Science
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    • v.34 no.1
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    • pp.96-100
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    • 2017
  • Amebic liver abscess (ALA) is the most common extraintestinal manifestation of amebiasis. Amebiasis, a parasitic infection caused by Entamoeba histolytica, used to be a prevalent protozoan disease in Korea, however, with an improving sanitary system, it has been among very uncommon etiology of liver abscess. A recent report suggested that ALA is an emerging parasitic infection in human immunodeficiency virus (HIV)-infected patients even in areas where the disease is not endemic and recommended HIV screening in patients in areas where ALA is not endemic, particularly those without history of travel to a disease-endemic area. We report on two patients who were admitted for treatment of ALA and then diagnosed as HIV infection. We also reviewed the etiology and characteristics of ALA in our hospital during the last 5 years.

L-Carnitine Reduces Obesity Caused by High-Fat Diet in C57BL/6J Mice

  • Mun, Eun-Gyeng;Soh, Ju-Ryoun;Cha, Youn-Soo
    • Food Science and Biotechnology
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    • v.16 no.2
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    • pp.228-233
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    • 2007
  • This study evaluated the effects of carnitine supplementation on obesity caused by a high-fat diet in C57BL/6J mice. The mice were fed a normal diet (ND), high-fat diet (HD), or carnitine-supplemented (0.5% of diet) high-fat diet (HDC) for 12 weeks. The results showed that body weight, energy intake, and feed intake were lower in the HDC group than the control groups. Acid-soluble acylcarnitine (A SAC), acid-insoluble acylcarnitine (AIAC), and total carnitine (TCNE) in the serum and liver were significantly higher in the HDC group. Hepatic carnitine palmitoyl transferase-I activity was significantly higher in the HDC group than the control groups. Acyl-coA synthetase (ACS) and carnitine palmitoyl transferase-I (CPT-I) mRNA expression in the liver was highest in the HDC group, however hepatic acetyl-coA carboxylase (ACC) mRNA expression in this group was lowest. Serum leptin levels and abdominal fat weight were lowest in the HDC group. We concluded that L-carnitine supplementation diminished the risk of obesity caused by a high-fat diet.

Analysis on Induced Current Density inside Human Body by 60 Hz ELF Magnetic Fields (60Hz ELF자계에 의한 인체내부 유도 전류밀도 해석)

  • Min Suk Won;Song Ki Hyun
    • Proceedings of the KIEE Conference
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    • summer
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    • pp.581-583
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    • 2004
  • This paper analysed the induced current density characteristics inside human body by extremely low frequency magnetic fields according to varying conductivities of human model. Human model was composed of several organs and other parts of 곳 human body, whose shapes were spheroids or cylinders. Organs taken into account were the brain, heart, lungs, liver and intestines. Applying the boundary element method to the human model, effects of the organ conductivity difference to the induced current distribution were estimated.

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The Increment of Purine Specific Sodium Nucleoside Cotransporter mRNA in Experimental Fibrotic Liver Induced by Bile Duct Ligation and Scission

  • Lee, Sung-Hee;Chae, Keon-Sang;Nan, Ji-Xing;Sohn, Dong-Hwan
    • Archives of Pharmacal Research
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    • v.23 no.6
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    • pp.613-619
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    • 2000
  • We investigated the expression profiles of rat fibrotic liver induced by bile duct ligation and scission (BDL/S) using the 3'-directed cDNA libraries. The possibility that the 3'-directed cDNA library represents the mRNA population faithfully was examined by northern blots. During the northern analysis based on fibrotic liver expression profile, we found for the first time that purine specific sodium nucleoside cotransporter (SPNT) was upregulated in BDL/S-induced fibrotic liver. To determine whether the accumulation of bile juice could affect the expression of SPNT mRNA or not, we examined the change of SPNT mRNA expression at 3, 14, 28 days after BDL/S operation. No change in SPNT expression was observed in rat liver at 3 days after surgery. In contrast, there were significant increases in SPNT expression at 14 and 28 days after surgery. We also examined whether chronic liver damage affected SPNT mRNA expression. SPNT mRNA level was significantly increased in BDL/S-induced fibrotic rat liver, whereas no significant change was obserbed in fibrotic livers chronically exposed to carbon tetrachloride or dimethylnitrosamine. From the above results, although further study might be needed, it was considered that the increment of SPNT mRNA in BDL/S liver morphological compatibility to human was remarkable.

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Insulin receptor substrate 2: a bridge between Hippo and AKT pathways

  • Jeong, Sun-Hye;Lim, Dae-Sik
    • BMB Reports
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    • v.51 no.5
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    • pp.209-210
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    • 2018
  • NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear. Here, we found that depletion of both PTEN and SAV1 in liver promotes spontaneous NAFLD and liver cancer through hyperactive AKT via YAP/TAZ-mediated up-regulation of IRS2 transcription. Conversely, NAFLD is rescued by both ablation of YAP/TAZ and activation of the Hippo pathway. Furthermore, human HCC patients with NAFLD showed strong correlation between YAP/TAZ and IRS2 or phospho-AKT expression. Finally, the inhibition of AKT by MK-2206 treatment attenuates NAFLD development and tumorigenesis. Our findings indicate that Hippo pathway interacts with AKT signaling during the intervention with IRS2 to prevent NAFLD and liver cancer.

Liver Fibrosis and Five Year Survival of Hepatocellular Cancer Cases Undergoing Transcatheter Arterial Chemo Embolization Using Small Doses

  • Li, Hong;Hu, Yaohong;Li, Na;Zhou, Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1589-1593
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    • 2012
  • Objective: To investigate liver fibrosis, TGF-${\beta}1$ levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super-selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-${\beta}l$ (TGF-${\beta}1$) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-${\beta}1$. Five year survival demonstrated no significant differences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.