• YAKHAK HOEJI
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• v.59 no.5
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• pp.201-206
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• 2015

The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.579-583
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• 2023

In human fetuses, the left hepatic artery (LHA) issues the marginal artery that runs along the umbilical vein and, sometimes, reaches the umbilicus. The further observation demonstrated that, in 5 of 12 Japanese midterm fetuses (crown-rump length mm: 46, 50, 54, 59, 102), the marginal artery issued not only a thin umbilical branch but also a liver parenchymal branch that took a posterosuperior recurrent course in a peritoneal fold and supplied the anterior surface of the liver left lobe (segment III). However, in 22 Spanish fetuses of which gestational ages corresponded to the Japanese ones, we did not find the parenchymal branch. Therefore, between human populations, there seemed to be a considerable difference in the incidence as to whether or not the marginal artery issues the liver parenchymal branch. The parenchymal branch might be degenerated at the later stages due to friction between the liver free surface and growing diaphragm.

• Journal of Microbiology
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• v.37 no.1
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• pp.41-44
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• 1999

Human mitochondrial aldehyde dehydrogenase 2 (ALDH2) is mainly responsible for oxidation of acetaldehyde generated during alcohol oxidation in vivo. A full-length cDNA of human liver ALDH2 was successfully expressed using a vaccinia virus-T7 RNA polymerase system. The expressed ALDH2 had an enzymatic activity as high as the native human liver ALDH2 enzyme.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2655-2661
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• 2014

Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and $LO_2$ cell line (p<0.05). Compared with the $LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.91-98
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• 2004

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) is a powerful carcinogen in several species, limited model system exist to study carcinogenicity of this compound at cellular level. To enhance our under-standing of carcinogenicity of TCDD at cellular level, we investigated micronucleus (MN) frequency as a index of genetic toxicity and whether TCDD can transform the human cells in culture. Normal human cell lines, skin keratinocyte HaCaT, Chang liver and breast MCF10A cells were used. TCDD did not affect the cell viability of the Chang liver, HaCaT and MCF10A cells. The frequency of micronucleus was increased after treatment of TCDD for 24hr in Chang liver and HaCaT cells, but not changed in MCF10A cells. And we observed putative transformed cells in Chang liver cells exposed to 1 $\mu$M TCDD for 2 weeks. The putative transformed cells were also observed in HaCaT cells with subsequent exposure to TCDD (0.1, 1, 10, 100 nM) for 2 weeks after initial exposure to MNNG, but not observed in MCF10A cells. Collectively, these results indicate that the ability of TCDD to induce micronuclei may be involved in cellular transformation of Chang liver and HaCaT cells. Our putative TCDD-transformed cells of Chang liver and HaCaT are expected to provide a clue to the elucidation of TCDD-induced transformation pathway.

• Journal of Biomedical Engineering Research
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• v.5 no.1
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• pp.55-62
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• 1984

A digital spectrum analysis technique was used to estimate the tissue characteristic parameters (transmission velocity and attenuation coefficient) in the phantom study and the human liver's ultrasound scanning. The soft tissue equivalent phantom was made with the combination materials of agar, water, powdered graphite, and n-propyl alcohol. In the human study, twenty five normal subjects and three patients with liver diseases were studied using the ultrasonic reflection signals and the spectrum analysis method The following results were obtained; 1. The soft tissue-equivalent materical could be produced with various acoustic parameters by changing the composition amount of the powdered graphite and n-propyl alcohol. 2. Attenuation coefficients of normal human liver tissue were estimated to be 0. 36 dB/cm MHz$\pm$0.11. In patients with liver disese, tile attenuation coefficients were shown to be different from the above normal values.

• Journal of Nutrition and Health
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• v.24 no.3
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• pp.199-205
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• 1991

Retinoic acid. the active metabolite of vitamin A. was detected in the human liver for the first time using a new method. A rapid and sensitive technique has been developed using gradient-elution. reverse-phase high performance liquid chromatography. This assay. with simultaneous multiwavelength detection at 294nm, 325nm and 450nm after saponifcation of liver samples. allows us seperation and quantitation of vitamin E, retinoic acid, total retinoids and various carotenoids in one small sample. The proportion of retinoic acid to total retinoids in human liver appears to be quite $consistent(2.4\pm0.2%$ ). With low vitamin A storage in liver, detection at another wavelenth 354nm would increase the sensitivity for retinoic acid of small quantity This method of analysis could be used for other tissues like red blood cells, plasma or serum, also. Hepatic retinoic acid level with total retinoids and carotenoids would serve a better indicator of functional vitamin A nutriture especially for those with disease requiring needle biopsy of liver.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• Food Science and Biotechnology
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• v.16 no.6
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• pp.894-901
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• 2007

This study investigated the effects of cell cultured Acanthopanax senticosus extract (ASE) supplementation and swimming exercise on lipid profiles and carnitine concentrations in C57BL/6J mice fed high fat diets. Male C57BL/6J mice (n=50), aged 4 weeks, were divided into 5 groups based on exercise and/or ASE supplementation (0.5 g/kg of body weight): normal diet (N-C), high fat diet (H-C), high fat diet non-supplement & exercise (H-NSE), high fat diet supplement & no exercise (H-SNE), high fat diet supplement & exercis (H-SE). Liver nonesterified carnitine (NEC) was significantly higher in the H-SNE group than in the H-C group, and liver total carnitine (TCNE) levels were significantly higher in the H-SNE group than in the H-NSE and H-SE groups. Liver and muscle carnitine palmitoyltransferase-I (CPT-I) mRNA levels tended to be higher with ASE supplementation and/or exercise. These results suggest that supplementation with ASE and/or exercise might have a role in improving lipid oxidation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5799-5804
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• 2012

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.