• Genomics & Informatics
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• v.21 no.4
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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.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.133-139
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• 2018

Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.122-128
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• 2024

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.147-158
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• 2016

The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Journal of Ginseng Research
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• v.41 no.4
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• pp.450-455
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• 2017

Chronic liver disease, one of the most common diseases, typically arises from nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for improved treatment strategies. Korean Red Ginseng has been known to have positive effects on liver disease and liver function. In this paper, we summarize the current knowledge on the beneficial effects of Korean Red Ginseng on chronic liver disease, a condition encompassing nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma, as supported by experimental evaluation and clinical investigation.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.13-20
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• 2005

Purpose : Obesity is, along with metabolic syndrome, closely related with nonalcoholic fatty liver disease. This study tried to evaluate the prevalence of nonalcoholic liver disease in obese children and verify the factors associated with the disease. Methods : Two hundred and seventy nine children who showed a body mass index of 95 percentile over the baseline in health examinations of surrounding schools were evaluated. Questionnaires, body measurements, blood examinations, and ultrasonographic measurements of abdominal fat were examined. Results : Out of 279 children enrolled for the study, 27 children were found to possess nonalcoholic liver disease(9.7%). Among those found to be positive for nonalcoholic liver disease, it's prevalence increased to 15.2%(22 out of 144 children) among children with severe obesity. Factors known to be involved with metabolic syndrome, namely waist/hip circumference ratio and thickness of abdominal fat, were found to be closely related to nonalcoholic fatty liver as well. Conclusion : The prevalence of nonalcoholic fatty liver in obese children was 9.7%, with higher incidence observable in severer obesity. Factors responsible for metabolic syndrome were closely associated with nonalcoholic fatty liver disease, and the level of insulin resistance, which is an useful index in both diseases, can be utilized in evaluation of the effect of treatment and control of risk factors.

• Journal of the Korean Society of Radiology
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• v.16 no.7
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• pp.943-952
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• 2022

As a test for diagnosing fatty liver, recently, ultrasound and blood exam are being performed simultaneously. In particular, in the case of high-sensitivity C-reactive protein in blood exam, it is used as an index indicating the level of inflammation in various parts of the body as well as cardiovascular diseases. Thus, this study was conducted to analyze the association between metabolic syndrome components, liver function, and high-sensitivity C-reactive protein levels according to the degree of nonalcoholic fatty liver, and use it as a clinical indicator for fatty liver diagnosis. Metabolic syndrome components, liver function and high-sensitivity C-reactive protein blood test values analyzed from 1,139 men and women over 20 years of age with nonalcoholic fatty liver in abdominal ultrasonography from March 2021 to August 2021 at the Korea Association of Health Promotion, Gwangju-Jeonnam Branch. Analyzed for all men and women, the blood test values for subjects with mild fatty liver were AST 30 U/L, ALT 32.1 U/L, γ-GTP 41.2 IU/L, and hs-CRP 0.14 mg/dL. These values were lower than the blood test values of subjects with moderate fatty liver (AST 38 U/L, ALT 47.6 U/L, γ-GTP 54.9 IU/L, hs-CRP 0.22 mg/dL) and was statistically significant (p<0.001). In this case of high-sensitivity C-reactive protein test, it is statistically significant, showing higher values in Subjects with moderate fatty liver than Subjects with mild fatty liver. thus, it is considered that hs-CRP can be used as clinical data for the prevention and management of fatty liver.

• The Korean Journal of Food And Nutrition
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• v.35 no.5
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• pp.332-342
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• 2022

Nonalcoholic fatty liver disease (NAFLD) is recognized one of the leading metabolic diseases globally, and the younger age population with the disease is rapidly growing, especially in developed countries. Since there has been no approved medicine, losing weight is known to be the only best remedy to control or reverse the disease. Recently, the field of microbiome has attracted much attention to offer more practical choices for patients. Here, we provide experimental evidence that Streptococcus thermophilus LM1012 (LM1012), a safe probiotic strain, is effective for improving NAFLD indexes. In the methionine-choline deficient (MCD) diet induced C57BL/6 mouse model, administration of LM1012 promoted marked reductions of aspartate transaminase (23.8%), total bilirubin (27.8%), hydroxycholesterol (64.2%), triglyceride (29.7%) and IL-1β (68.3%) compared to the MCD diet alone group. Also, the histopathological data imply that LM1012 inhibited fat accumulation and inflammation in the liver, which are the key biomarkers for progression of the disease. Together, these findings suggest that human consumption of LM1012 as a healthy nutritional supplement, may be helpful in reducing the risk of liver damages in NAFLD patients.

• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.19-25
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• 2013

Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.