• Yonsei Medical Journal
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• v.59 no.9
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• pp.1064-1071
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• 2018

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

• BMB Reports
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• v.55 no.10
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• pp.481-487
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• 2022

Over the past few years, hydrogen sulfide (H₂S) has been shown to exert several biological functions in mammalian. The endogenous production of H₂S is mainly mediated by cystathione β-synthase, cystathione γ-lyase and 3-mercaptopyruvate sulfur transferase. These enzymes are broadly expressed in liver tissue and regulates liver function by working on a variety of molecular targets. As an important regulator of liver function, H₂S is critically involved in the pathogenesis of various liver diseases, such as non-alcoholic steatohepatitis and liver cancer. Targeting H₂S-generating enzymes may be a therapeutic strategy for controlling liver diseases. This review described the function of H₂S in liver disease and summarized recent characterized role of H₂S in several cellular process of the liver.

• Korean Journal of Veterinary Research
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• v.53 no.3
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• pp.169-174
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• 2013

We demonstrated that a mineral aqueous solution (MAS) administered to mice functionally and histologically protected against cisplatin-induced acute renal failure (ARF) and $CCl_4$-induced acute liver failure (ALF). In ARF model, 0.4 and 0.2% MAS decreased mortality and the serum concentrations of blood urea nitrogen (BUN) and creatine in mice. Additionally, 0.4 and 0.2% MAS reduced contraction of distal convoluted tubules and suppressed expression of the proinflammatory cytokines interlukein-6 (IL-6) and tumor necrosis factor (TNF-${\alpha}$) in the kidney. In ALF model, 0.4 and 0.2% MAS decreased serum concentrations of alanine aminotransferase and aspartate aminotransferase in mice. Additionally, 0.4 and 0.2% MAS reduced necrotic areas and suppressed expression of IL-6 and TNF-${\alpha}$ in the liver. These results indicate that a MAS might have protective effects against ARF and ALF.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.343-349
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• 2013

This article is a study on to which categories of modern diseases blood deficiency pattern types are assigned by reference to modern clinical papers. Clinical papers were searched in China National Knowledge Infrastructure(CNKI) from 1994 to 2013. Results are as follows. First, diverse diseases classified in qi-blood depletion pattern and pattern of blood deficiency and wind-dryness are reported and pattern types designated by the name of viscera are the minority. Second, among pattern types in Korean Standard Classification of Diseases(KCD), diseases classified in heart blood deficiency pattern, liver blood deficiency pattern and heart-liver blood deficiency pattern are a few. Third, the level of designation by the combined patterns such as qi deficiency, fluid deficiency, yin deficiency, kidney deficiency, essence deficiency, wind-cold, cold-dampness, dampness-heat, liver hyperactivity, liver depression and static blood is more specific than KCD, which makes pattern types more useful to clinical application. The detailed relation between modern diseases and pattern types can be an another topic.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.116-125
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• 2005

Orthotopic liver transplantation is the treatment of choice for inherited metabolic diseases. However, the supply of donor organs is limiting and therefore many patients cannot benefit from this therapy. In contrast, hepatocytes can be isolated from a single donor liver. They can be transplanted into several recipients, and this procedure may help overcome the shortage of donor livers. A great deal of work with animal models indicates that hepatocytes transplanted into the liver or spleen can survive, function, and participate in the normal regenerative process. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to whole organ transplantation and for providing metabolic support during liver failure and for replacing whole organ transplantation in certain inherited metabolic diseases. Nowadays, hepatocytes from various stem cells have been regarded as an another cell source for treatment of inherited metabolic diseases. Although cell therapy using stem cells for inherited metabolic disease patient has been accepted only as an experimental trial yet, hepatocytes from stem cells can solve a lot of obstacles in the treatment of inherited metabolic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6945-6948
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• 2014

Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients. Materials and Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed. Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia. Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1779-1782
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• 2012

Background & Objectives: In patients with gastric cancer, the most frequently reported family history of cancer also involves the stomach. The aim of this study was to assess the presence of gastric precancerous lesions in first-degree relatives of patients with gastric cancer and to compare the obtained results with those of individuals with no such family history. Methods: Between 2007 and 2009, 503 consecutive persons more than 30 years old were enrolled in the study covering siblings, parents or children of patients with confirmed adenocarcinoma of stomach. The control group was made up of 592 patients who were synchronously undergoing upper gastrointestinal endoscopy for evaluation of dyspepsia without gastric cancer or any family history. All subjects were endoscopically examined. Results: The overall prevalence of Helicobacter pylori was 77.7% in the cancer relatives and in 75.7% in the control group. Chronic gastritis was found in 90.4% vs. 81.1% (P<0.001). Regarding histological findings, 37(7.4%) of the study group had atrophy vs. 12(1.7%) in the control group (P<0.001), while no difference was observed for intestinal metaplasia (20.3%vs. 21.6%, P=0.58). Dysplasia were shown in 4% of cancer relatives but only 0.4% of the control group (P<0.001). There was no gender specificity. Conclusions: Findings of our study point to great importance of screening in relatives of gastric cancer patients in Iran.

• Natural Product Sciences
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• v.17 no.3
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• pp.165-174
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• 2011

Naturally occurring small molecules from plants, microorganisms, and animals allow the design of drugs that can be beneficial in virtually all kinds of human diseases. Liver diseases with diverse etiologies such as viral infection, chemical intoxication, and metabolic fat accumulation are one of the leading causes of human mortality. Unfortunately, however, there are few effective drugs available capable of stopping or reversing the progress of liver disease. Here, we discuss the current advances in developing hepatoprotective natural products for several arrays of liver disease pathogenesis.

• Genomics & Informatics
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• v.11 no.3
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• pp.149-154
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• 2013

Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.

• Parasites, Hosts and Diseases
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• v.54 no.4
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• pp.519-525
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• 2016

To investigate the potential role of transforming growth factor (TGF)-${\beta}1$ in liver fibrosis during Echinococcus granulosus infection, 96 BALB/c mice were randomly divided into 2 groups, experimental group infected by intraperitoneal injection with a metacestode suspension and control group given sterile physiological saline. The liver and blood samples were collected at days 2, 8, 30, 90, 180, and 270 post infection (PI), and the expression of TGF-${\beta}1$ mRNA and protein was determined by real-time quantitative RT-PCR and ELISA, respectively. We also evaluated the pathological changes in the liver during the infection using hematoxylin and eosin (H-E) and Masson staining of the liver sections. Pathological analysis of H-E stained infected liver sections revealed liver cell edema, bile duct proliferation, and structural damages of the liver as evidenced by not clearly visible lobular architecture of the infected liver, degeneration of liver cell vacuoles, and infiltration of lymphocytes at late stages of infection. The liver tissue sections from control mice remained normal. Masson staining showed worsening of liver fibrosis at the end stages of the infection. The levels of TGF-${\beta}1$ did not show significant changes at the early stages of infection, but there were significant increases in the levels of TGF-${\beta}1$ at the middle and late stages of infection (P<0.05). RT-PCR results showed that, when compared with the control group, TGF-${\beta}1$ mRNA was low and comparable with that in control mice at the early stages of infection, and that it was significantly increased at day 30 PI and remained at high levels until day 270 PI (P<0.05). The results of this study suggested that increased expression of TGF-${\beta}1$ during E. granulosus infection may play a significant role in liver fibrosis associated with E. granulosus infection.