• Journal of Applied Biological Chemistry
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• 제66권
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• pp.159-164
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• 2023

Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.

• Biomolecules & Therapeutics
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• 제30권2호
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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.

• Journal of Preventive Medicine and Public Health
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• 제27권4호
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• pp.747-761
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• 1994

Workers' periodic health examination is the main tools used to manage the health problems of most workers in Korea. The most common health problem found in workers' periodic health examination is liver disorder. Liver disorder is also one of the most common health problems in general population and one of the leading causes of mortality in adult population. Regulation proposed by government (No. 207, Ministry of Labor, 1992) defines the criteria for selection of workers with the liver dysfunction for further evaluative examination and the examination items used for diagnosis of the workers with liver dysfunction. This study was designed to evaluate the proficiency of each examination items presently defined in Regulation and propose the optimal examination items for detection of the liver disorders found by workers' periodic health examination. Study subjects are 186 workers with abnormal liver function tests in screening examination of workers' periodic health examination. Questionnaire survey including past history of liver disorder, drinking history, height and weight was done. Physical examination by physician, routine test items defined by Regulation (SGOT, SGPT, $\gamma$-GTP, protein, albumin, total and direct bilirubin, alkaline phosphatase, $\alpha$-feto protein, HBsAg and anti-HBs), anti-HCV antibody test and liver ultrasonography were done. Results are as follows; 1. Result of evaluative examination utilizing only the items defined in Regulation was; There were 75 workers with suspected live. disorder(40.3%), 63 with no liver dysfunction (33.9%), 13 with suspected hepatitis B(7.0%), 10 workers with hepatitis B(5.4%), 10 workers with hepatitis B carrier state(5.4%), 10 with alcoholic liver disorders(5.4%), 5 with fatty liver(2.7%). When alternative diagnostic criteria applying additional examination items (drinking history, body mass index, anti-HCV antibody and ultrasonography) diagnosability of liver disorder was increased. When all four items were included, final results were; 23 workers (17.8%) with hepatitis B (10 carriers, 13 suspects and 10 hepatitis B), 10 (5.4%) with hepatitis C(4 carriers, 5 suspects and 1 hepatitis C), 13(7.0%) with alcoholic liver disorder, 45(24.2%) with fatty liver (40 suspects, 5 fatty liver), 410%) with suspected liver disorders and 44 (23.7%) with normal liver. 2. Of examination items defined by Regulation, only SGOT, SGPT, $\gamma$-GTP and HBsAg were significantly different in abnormal rate and mean value, and all other laboratory findings did not showed significant difference between two groups. Drinking history, body mass index and anti-HCV antibody test which are the items that authors included in this study, also showed significant difference between two groups. Utilization of body mass index (BMI) for abnormal liver function group in diagnosis of fatty liver had high specificity (97.6%) but sensitivity (22.3%) was low. Therefore we suggest that SGOT, SGPT, $\gamma$-GTP, HBsAg, alcohol drinking history, BMI and anti-HCV Ab were useful for diagnosis of liver disorders among worker's periodic health examination.

• 동의생리병리학회지
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• 제16권4호
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• pp.630-636
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• 2002

After The Yellow Emperor's Canon of Internal Medicine, The text researches of pathologic change to the liver disease concluded the next, 1, The category of liver-disease(肝病) include the Symptoms of abnormality due to vital energy and blood motion, emotion and intention, muscular and reproductive function, and legions around descending liver channel. 2. In the theory that Liver-Yang energy(肝陽氣) is always overproducing, Liver-Yin blood(肝陰血) is always lacking, pathologic characteristics for liver disease is functional change of malfunction of the use of body(體用失調), So nourishing the liver and kidney is used for the principal aspects of a disease. regulating and calm the liver is used for the secondary aspects of a disease as the treatment plan, 3. If malfunctioning of the functions of dispersion and discharge(疏泄), Iiver-energy(肝氣) is becoming degected, So overproduct and overflow of ascent and exhalation of liver-yang(肝陽) is becoming blood are ascending following energy. complete usage of Yin-blood(陰血) is responsible for some kinds of mass formed by blood stasis in the early stage of pathogenesis of liver disease syndrome of the energy system as the progession of disease extravasated blood is forming. the pathologic characteristics is appeared loss of control of the vital energy and blood(體用失調) at the liver disease. 4. Sthenia-syndrome of liver(肝實證) and liver-heat syndrome(肝熱證) is appered that overproducing and overflow of dispersion(疏泄太過) and discharge is responsible for overfunctioning of liver disease or some kinds of heat syndrome such as liver fire(肝火), Sthenia of liver-yang(肝陽上亢), the syndromes of sthenic liver heat(肝實熱) are appered. deficiency of the liver(肝虛證) and cold syndrome of liver(肝寒證) is classified pathologic characteristics of cold and heat, deficiency and excess that regression of sensory, motor, mental due to lack of dispersion and discharge(疏泄不及), or intruding of the cold miasma, are degected. 5. The liver is close relation of physiologic function and internal organ such as spleen, stomach, lung, heart, kidney, gall bladder by the meridian channels, because of property of wind Zang, rapid progession is classified by phthologic charateristics.

• Journal of Nutrition and Health
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• 제30권1호
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• pp.48-60
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• 1997

The purpose of this study was to evaluate alcohol consumption and nutritional status in patients with alcoholic liver disease. The subjects were 80 patients with alcoholic liver cirrhosis and 12 patients with alcoholic fatty liver. Also 57 alcoholics without liver disease, 32 patients with viral liver cirrhosis and 194 normal men were included as control groups. Data on anthropometric index, socioeconomic status, alcohol consumption, dietary habits and dietary intakes were collected by individual interview. Alcoholic liver disease group had significantly lower triceps skinfold thickness and mid-uppr-arm circumferences than other groups. Socioeconomic status of alcholoci subjects was middle class or lower than that. The amount, duration and frequency of alcohol consumption were significantly higher and the quality of side dishes consumed with alcoholic beverage was significantly poorer in patients with alcoholic liver cirrhosis than others. Patients with alchololic liver disease ingested approximately 40% of daily caloric intake as alcohol and all alcoholic subjects had lower average intakes of protein, carbohydrates, fat, vitamins and minerals as compared with Korean adult average intakes. The results suggest that alcohol and poor dietary intake could cause malnutrition and might be two of the important risk factors to develop alcoholic liver disease in alcoholics. But other factors like genetic and immunological factors should be also considered in elucidating the causes of alcoholic liver disease. An extensive nutritional education should be emphasized for alcohol consuming population to prevent development of alcoholic liver disease.

• 대한한의학방제학회지
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• 제22권1호
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• pp.193-200
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• 2014

Objective : The purpose of this study is to report that patient diagnosed as drug-induced liver injury treated with herbal and western medicine improve liver function test. Methods : We treated the patient diagnosed as drug-induced liver injury caused by antibiotics with Hepatotonics and Cheonggan-tang Gagam(淸肝湯加減). Then, We followed up the result of liver function test. After the result of liver function test improved, we diagnosed the patient with Korean medical methods, and evaluated the symptom of Cerebral infarction and liver function test treating the patient with Jihwangumja (地黃飮子). Result : After our treatment, Liver function test and symptoms of Cerebral infarction result improved. Conclusion : Use of Western medicine with herbal medicine can improved liver function test of drug-induced liver injury effectively and herbal medicine do not disturb the liver function.

• Journal of Yeungnam Medical Science
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• 제18권1호
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• pp.1-12
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• 2001

Liver transplantation is widely accepted as an effective therapeutic modality for a variety of irreversible acute and chronic liver diseases for which no satisfactory therapy is available. Following the first unsuccessful efforts at human liver transplantation in 1963, development of the procedure evolved at first slowly and steadily for 20 years and then rapidly over the past two decades. The growth of liver transplantation was facilitated by the conclusion of the national institutes of health consensus development conference in 1983 that liver transplantation is not an experimental procedure but an effective therapy that deserves broader application. The number of liver transplantations increased 2.4-fold(from 1.713 to 4.058) from 1988 to 1996. but the number of patients on the UNOS(united network of organ sharing) liver list increased 12.1-fold(from 616 to 7,467); as would be expected, the number of deaths of listed patients increased 4.9-fold(from 195 to 954), The current supply of donor livers is insufficient to meet this need, and organ donation has been stagnant or increased by only a few percent in recent years. These facts underscore the importance of the appropriate selection of candidates for liver transplantation and the development of operative procedures, such as living donor liver transplant, split liver transplant and auxiliary partial liver transplant.

• Genomics & Informatics
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• 제21권4호
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• pp.45.1-45.11
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• 2023

Nonalcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease, with severity levels ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). The extent of liver fibrosis indicates the severity of NASH and the risk of liver cancer. However, the mechanism underlying NASH development, which is important for early screening and intervention, remains unclear. Weighted gene co-expression network analysis (WGCNA) is a useful method for identifying hub genes and screening specific targets for diseases. In this study, we utilized an mRNA dataset of the liver tissues of patients with NASH and conducted WGCNA for various stages of liver fibrosis. Subsequently, we employed two additional mRNA datasets for validation purposes. Gene set enrichment analysis (GSEA) was conducted to analyze gene function enrichment. Through WGCNA and subsequent analyses, complemented by validation using two additional datasets, we identified five genes (BICC1, C7, EFEMP1, LUM, and STMN2) as hub genes. GSEA analysis indicated that gene sets associated with liver metabolism and cholesterol homeostasis were uniformly downregulated. BICC1, C7, EFEMP1, LUM, and STMN2 were identified as hub genes of NASH, and were all related to liver metabolism, NAFLD, NASH, and related diseases. These hub genes might serve as potential targets for the early screening and treatment of NASH.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7101-7106
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• 2013

Background: The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ${\leq}$ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. Methods: A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. Results: After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ${\leq}$ 1-year) of HCC meeting Milan criteria. Conclusions: AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

• 대한한의학회지
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• 제31권2호
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• pp.109-113
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• 2010

Objectives: Liver function tests are used as screening tests for liver injuries, but their inaccuracy on positive predictive values can result in numerous false positive results. We investigated the incidence of liver function test abnormalities of patients who came to an oriental medicine hospital, in order to present a practical way to rule out false positive results for other studies designed to investigate the safety of Korean herb medicine. Methods: We analyzed the medical records and liver function test results proceeded at admission of all in-patients admitted to Jaseng Oriental Medicine Hospital, from July 2008 to June 2009. Results: Among 1,117 inpatients, 941 executed liver function tests on admission, and 40 were excluded due to their diagnosed liver disease. 747 (82.9%) of 901 enrolled patients were within the normal range of all liver function tests, and 140 (15.5%) and 14 (1.6%) were classified as "abnormalities of liver tests" and "liver injury" respectively, according to the CIOMS (Council for International Organizations of Medical Sciences) criteria. Conclusions: According to the results, among the outcomes of liver function tests proceeded among the patients admitted to the oriental medicine hospital, excluding who were diagnosed with liver disease, 17.1% showed abnormality. This means simple liver function test results are not sufficient in determining liver toxicity of Korean herb medicine (KHM).