• BMB Reports
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• 제40권5호
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• pp.814-824
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• 2007

Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

• 한국임상수의학회지
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• 제38권4호
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• pp.179-183
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• 2021

A 12-year-old male American Cocker Spaniel was diagnosed with a type of chronic hepatits (CH) called cholangioheaptits. Routine supportive medication was administered to the patient, and ex vivo boosted immune cell (EBI-C) therapy was used for the treatment. A histopathologic examination of the liver 19 months later revealed that the cholangiohepatitis had progressed to cholangiocarcinoma. The medication and immune cell therapy was maintained. Two months after the new diagnosis, the patient's state worsened, and the dog died 635 days after the first visit. EBI-C therapy is a type of immunotherapy, where immune cells are isolated from the patient's peripheral blood mononuclear cells, expanded ex vivo, and then infused into the patient intravenously every two weeks. EBI-Cs (mean: 2.78 × 10⁸ cells) were obtained 38 times and infused every two weeks. Most EBI-C were T-lymphocytes (99.24% of total EBI cells). T-lymphocytes produce large interferon (IFN)-γ, and IFN-γ inhibits liver fibrosis in dogs with CH. Moreover, in bile duct cancer, an increase in T-lymphocytes correlates with decreasing tumor invasion and metastasis. Thus, we propose that EBI-C therapy is applicable as a new supportive therapy for canine liver disease if other treatments like drug medication, surgery, or radiation are unavailable.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

• BMB Reports
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• 제37권6호
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• pp.741-748
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• 2004

The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

• Pediatric Infection and Vaccine
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• 제11권2호
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• pp.153-157
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• 2004

목 적 : TTV는 인체 감염이 확인된 최초의 circovirus로 간염을 유발할 가능성에 대해 연구가 이루어지고 있다. TLMV는 최근에 발견된 circovirus로 TTV보다 작지만 유사한 구조를 가진 것으로 알려져 있다. TLMV 감염의 성인 유병률은 약 70%인 것으로 알려지지만 소아의 유병률은 아직 확실하지 않다. 이에 저자들은 국내 소아의 TLMV 유병률을 알아보기 위하여 시행하였다. 방 법 : 2001년 6월부터 12월까지 인제의대 상계 백병원 외래를 방문한 환아중 TTV DNA에 대한 PCR이 시행되었던 88명의 혈청 검체를 대상으로 하였다. TLMV의 5'NCR(noncoding region) 특이적 시발체를 이용하여 PCR을 시행하였다. 1라운드 PCR은 M1359, M1365 시발체를 사용하여 $94^{\circ}C$ 10분, $94^{\circ}C$에서 40초, $60^{\circ}C$에서 40초, $72^{\circ}C$에서 50초, $72^{\circ}C$에서 10분의 조건에서 55회 시행하였다. 최종 산물 $2{\mu}L$에 M1360, M1366 시발체를 사용하여 1라운드와 동일한 조건에서 PCR을 55회 시행하였다. TLMV PCR 양성이 나온 10건에 대해 직접 염기 서열 분석과 계통 분석을 시행하였다. 결 과 : 소아 전체 연령에서 TLMV 감염 유병률은 49%였다. 연령별 유병률은 생후 1세 미만은 36%, 1~3세는 62%, 4~6세는 43%, 7~9세는 16%, 10~15세는 66%였다. 전체 소아의 22%에서 TTV와 TLMV의 혼합 감염이 확인되었다. TLMV PCR 산물 10건에 대한 염기 서열 분석을 시행한 결과 다른 나라의 TLMV 염기 서열과 많은 차이가 났다. 결 론 : 국내 소아의 TLMV 유병률은 49%로 비교적 높았으며 TLMV와 TTV와 혼합 감염이 발생함을 알 수 있었다. 국내에서 유행하는 TLMV의 유전형이 다른 나라와 큰 차이가 있을 가능성이 있지만 이에 대한 연구가 더 필요할 것으로 보인다.

• 한국동물학회지
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• 제26권3호
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• pp.211-217
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• 1983

한국인집단에서 Transferrin C subtypes와 Haptoglobin polymorphism의 분포 및 유전자 빈도에 관한 본 연구에서 얻은 결과는 다음과 같다. 제주집단에서 관찰된 Transferrin C subtypes은 주로 $T_{f}C_{1}, T_{f}C_{2}$ 및 $T_{f}C_{1}-C_{2}$형이었는데 $T_{f}C_{1}$과 $T_{f}C_{1}-C_{2}$이 51%와 42%로 나타났으며, 유전자 빈도는 $T_{f}C^{1}, T_{f}C^{2} 및 T_{f}D^{Jeju}$가 각각 0.7220, 0.2743 및 0.0037이었다. Haptoglobin의 유전자 빈도는 서울집단에서 460명, 제주집단에서 502명을 대상으로 추정한 결과 서울집단에서 $Hp^1 = 0.304, Hp^2 = 0.696$이었고, 제주집단에서는 0.269와 0.731이었으며 두 집단사이에 빈도 차이는 유의하지 않았다.

• 대한본초학회지
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• 제38권4호
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• pp.31-43
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• 2023

Objectives : The objective of this study was to investigate the phytochemistry and pharmacological activities of Cirsium setidens. Methods : Domestic and international articles about Cirsium setidens were investigated. A review was perfoemed via DB searching engine such as Sci.Direct, Springer, DBpia, KISS, Google scholar, Kipris, and so on. Total 73 listed literature were classified by compound analysis and pharmacological efficacy. Results : C. setidens contains pectolinarin and its glycoside, pectolinarigenin as index compounds, and linarin, apigenin, diosmetin, scopoletin, acacetin, cirsimarin, cirsimaritin, setidenosides A and B, silymarin, hispidulin, 92 volatile compounds, and 15 fatty acids. The Pharmacological activities of C. setidens has been reported to inhibit of platelet aggregation and fat accumulation in the liver, inhibit to hepatitis, anti-cancer, antibacterial, skin improvement, hair growth, liver protection, anti-diabetic, anti-inflammatory, sedative. Also, It has been reported the effect of cholesterol-lowering and anti-obesity, neuroprotective effects, increasing human stem cell viability, inhibiting osteoclast formation and osteogenic differentiation. Conclusion : This reviews showed that C. setidens which has been traditionally used for the treatment of inflammation and hypertension, has anticancer and river protective effect, as well as hair loss and diet. In order to maximize the efficacy of C. setidens, research has also begun on the effect of processing processes such as fermentation or fine powdering and combining natural plant resources.

• BMB Reports
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• 제51권1호
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• pp.33-38
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• 2018

Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased intracellular TG levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription by directly binding to the SREBP1c promoter (at the -139- to +359-bp region). Moreover, we observed that HCBP6 interacted with $C/EBP{\beta}-binding$ site in the SREBP1c promoter both in vitro and in vivo. These results indicate that HCBP6 upregulates human SREBP1c expression by binding to the $C/EBP{\beta}-binding$ site in the SREBP1c promoter.

• 대한임상검사과학회지
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• 제50권3호
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• pp.261-266
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• 2018

만성C형 간염환자 160예를 대상으로 immunoblot방법과 RT-PCR-hybridization법을 실시하여 임상검사의 유용성을 알아보았다. 양성 150예 중 133예만 RT-PCR-hybridization 법에서 양성을 나타내어 immunoblot법의 진양성율은 88.6%를 나타났으며 두 방법 간의 일치율은 89.3%를 나타났다. 한국인의 HCV 아형을 알기 위하여 혈청형과 유전형을 실시하였다. HCV혈청형 1형과 2형 그리고 1b와 2a유전형이 가장 많은 C형간염 감염원으로 나타났다. 49예를 혈청형과 유전형을 서로 비교한 결과, 혈청형 검사에서 28예(57.1%)가 1형, 21예(42.9%)가 2형으로 나타났으며 유전자형 검사에서 1b형이 25예(51.0%), 1b/2b를 나타낸 예가 1예(2.0%), 2a형이 17예(34.7%), 2a/2c를 나타낸 예가 4예(8.2%), 그리고 2b형이 2예(4.1%)로 나타났다. 본 연구에서는 HCV 간이검출법으로는 immunoblot방법이 유용하며, immunoblot방법 양성 확진검사로는 RT-PCR-hybridization법을 실시하였다. 혈청형이 C형간염의 치료 나 진행과정을 관찰하기 위해서는 유전형보다 유용하나 인터페론 치료효과는 1형과 2형 혈청형별에 따라 차이를 보이지 않았다.

• 한국식품위생안전성학회지
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• 제24권1호
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• pp.19-26
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• 2009

본 연구는 집단급식 안전성 확보 및 식중독 방지를 위해 단체급식 안전성에 관하여 전문가를 대상으로 국내 집단급식 식중독 원인을 조사하고, 미래 집단급식 식중독 발생을 예측하였다. 델파이 설문 결과 국내 집단급식 식중독 원인은 '식재료 위생관리 미흡', '손세척', '구역구분', '유통업체 보관' 등이 가장 크게 영향을 주는 것으로 나타났다. 미래 집단급식 식중독 발생 예측 조사 결과 Vibrio parahaemolyticus, Escherichia coli(EPEC), non-typhoid Salmonella serotypes, Staphylococcus aureus, Escherichia coli(ETEC), Norovirus, hepatitis A virus가 지속적으로 식중독을 발생시킬 것으로 예측하였으며, 집단급식에서 식중독 유발 가능성이 높은 식재료로는 영유아(1-6세), 초등학생(7-12세), 중 고등학생(13-19세)의 식재료 섭취량과 식중독 유발 가능성을 고려해 볼 때 '과일류', '우유', '생선류', '돼지고기', '계란', '쇠고기'였으며, 식단 메뉴로는 '비빔밥', '콩나물무침', '시금치나물', '오이생채', '잡채', '돼지불고기'가 위해도가 높을 것으로 예측되었다. 집단급식소에서 사용빈도가 높을 것으로 예측된 가공식품은 '냉동, 냉장보관식품' 이었으며, 살균방법은 '가열처리', '화학적 살균소독제'로 나타났다. 저장법은 '냉장($10^{\circ}C$ 이하)', '냉동($-20^{\circ}C$ 이하)'법이, 배식형태는 '집단급식소에서 직접 배식' 형태가 집단급식소에서 향후 사용빈도가 높을 것으로 예측되었다. 본 설문조사 결과는 집단급식 전 과정의 체계적인 위생관리시스템의 도입과 식중독예방 식단 구성을 위한 기초자료로 활용될 것으로 사료된다.