• 대한임상검사과학회지
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• 제43권4호
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• pp.194-204
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• 2011

This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.

• Nutrition Research and Practice
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• 제14권4호
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• pp.334-351
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• 2020

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

• Journal of Gastric Cancer
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• 제7권4호
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• pp.254-260
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• 2007

목적: 위와 소장에 발생한 위장관 간질종양의 임상병리학적 특징을 비교하여 예후 인자 및 적절한 치료의 방침을 알아보고자 하였다. 대상 및 방법: 대진의료재단 분당제생병원에서 1998년 8월부터 2006년 5월까지 위장관 간질종양으로 진단된 38명의 환자 중 분석 및 추적 조사가 가능했던 29명의 환자에서 임상 양상을 조사하고, 면역조직화학적 염색을 시행하였으며, NIH 합의안에 따라 위험도를 분류하여 각각 위와 소장에서 발생한 위장관 간질종양을 비교하였다. 결과: 위와 소장에 발생한 위장관 간질종양의 임상병리학 적 차이 및 재발 양상의 차이는 없었으며, NIH 위험도 분류에 따라 나눈 고위험군과 저위험군 간에 재발의 차이는 있었다(P=0.030). 결론: 위장관 간질종양에서 원발 부위인 위와 소장간에 임상병리학적 양상이나 예후에 통계학적으로 유의한 차이는 없었으나, NIH 분류에 의한 고위험군에서는 재발 가능성이 높으므로 치료 지침에 따른 적절한 추적관찰이 필요하며, 앞으로 여러 기관의 예를 통합한 큰 모집단을 대상으로 지속적인 연구를 시행하여 국내 실정에 맞는 정확한 진단 기준 및 치료지침이 만들어져야 될 것으로 사료된다.

• Molecules and Cells
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• 제40권6호
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• pp.386-392
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• 2017

Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, ${\alpha}-smooth$ muscle actin, platelet-derived growth factor receptor ${\beta}$, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the $SDF-1{\alpha}$ and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.320-327
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• 2020

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

• 대한임상검사과학회지
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• 제36권2호
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• pp.163-172
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• 2004

Mast cells (MCs) have been implicated in the pathogenesis of tissue fibrosis. However, the role of MC in the development of liver fibrosis has not been fully elucidated. Stem cell factor (SCF) is known to recruit MCs to the liver following injury as it induces mast cell proliferation, survival and differentiation from resident tissue precursors. This study examines the interaction between activated hepatic stellate cells (HSCs) and MCs in rat fibrotic liver, and SCF production by HSCs during culture in vitro. Rats were studied 4, 7, 14 and 21 days after bile duct ligation (BDL). Fibrogenesis was assessed by a measurement of collagen stained with sirius red F3B. Activated HSCs and MCs were identified by ${\alpha}$-smooth muscle actin (${\alpha}-SMA$) immunohistochemical and alcian blue staining and measured by a computerized image analysis system. SCF production was determined in rat HSC cultures using Western blotting. Mild fibrotic changes were noted in BDL rat livers as early as 4 days after induction of cholestasis. Significant expansion and organization of fibrous tissue has occurred in day 14 BDL rats which progressed to bridging fibrosis by day 21. In BDL rats, both a large number of activated HSCs and MCs were detected in portal tracts and fibrous septa. Both area of activated HSCs infiltration and density of MCs were significantly higher in all BDL group compared with Shams. In BDL rats, both areas of activated HSCs infiltration and density of MCs were no significant difference between day 4 and 7 and were significantly higher in day 14. However, the areas of activated HSCs infiltration were significantly lesser in day 21 and the densities of MCs were significantly higher in day 21 compared with day14 BDL. In BDL rats, both areas of activated HSCs infiltration and density of MCs were highly correlated with areas of fibrosis. Western blotting showed that SCF protein was consistently produced in activated HSCs by culture on plastic and freshly isolated HSCs expressed relatively little 30kD SCF compared to late primary culture activated HSCs (day 14) and passaged HSCs. These results suggest that HSCs activated in vitro produce SCF, and may play an important role in recruiting mast cells to the liver during injury and fibrosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권2호
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• pp.81-93
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• 2006

Obstructive sialadenitis is one of common disease in salivary gland, and most common histologic features are loss of acinar cell and ductal dilatation associated with fibrosis, and infiltration of inflammatory cells. Although many experimental studies has been accomplished for the salivary acinar cell change in obstructive salivary gland disease, studies for myoepithelial cell were deficient. This study is designed for salivary gland tissue change, especially myoepithelial cell when nonspecific chronic sialadenitis or salivary duct injury by duct obstruction or cut can be occurred that is common encounted clinically. After ligation and cutting of submandibular gland of rabbit, groups of aminmal were sacrificed at 1, 2, 4 weeks postoperatively, submandibular gland were removed. The histopathologic evaluation was done with light microscopy. And, with immunohistochemical staining with ${\alpha}$-smooth muscle actin, characteristics of myoepithelial cell were examined. With transmission electron microscopy, ultrastructure of myoepithelial cell were examined for distribution and ultrastructure of myoepithelial cell. The results were obtained as follows: 1. In the histopathologic evaluation, ligation and cutting group of 1 week, linkage of myoepithelial cell associated with acinar atrophy and degeneration were disappeared in both group. 2. More prominent squamous metaplasia was seen in acinar cells of ligation group of 2 weeks experimental rabbit than cutting group. 3. Acinar cells are nearly disappeared in both ligation and cutting group of 4 weeks, and myoepithelial cell also disappeared associated with acinar cell atrophy, and duct-like structure composed by squamous cells by squamous metaplasia in acinar cells were distributed. 4. In immunohistochemical study, both ligation and cutting group ${\alpha}$-SMA distribution were diminished at 1 week experimental rabbits, but myoepithelial cell was more diminished in ligation group than cutting group, which were distributed around cells of squamous metaplasia. 5. Nuclear condensation, chromosome margination, and cytoplasmic vaculoation were appeared in myoepithelial cell of both cutting and ligation group after 1 week with transmission electron microscopy. But degenerative substance were seen in cytoplasm of myoepithelial cell of ligation group of 4 weeks. From the results obtained in this study, atrophy and degeneration of myoepithelial cell was more prominent in duct ligation group than duct cutting group, and myoepithelial cells were seen around cells squamous metaplasia of acinar cell.

• Journal of Periodontal and Implant Science
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• 제36권3호
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• pp.613-625
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• 2006

Periodontal ligament(PDL) cells and human gingival fibroblasts(HGFs) play important roles in development, regeneration, normal function, and pathologic alteration. PDL cells and HGFs have the similarity related with general characteristics of fibroblast such as spindle shaped morphology, the presence of vimentin intermediate filament and the synthesis of interstitial collagens and fibronectin. There were many studies about the differences between PDL cells and HGFs, but they were not about whole gene level. In this study, we tried to explain the differences of gene expression profiles between PDL cells and HGFs, and the differences among three individuals by screening gene expression patterns of PDL cells and HGFs, using cDNA microarray. Although there were some variants among three experiments, a set of genes were consistentely and differentially expressed in one cell type. Among 3,063 genes, 49 genes were more highly expressed in PDL cells and 12 genes were more highly expressed in HGFs. The genes related with cell structure and motility were expressed more highly in PDL cells. These are cofilin 1, proteoglycan 1 secretory granule, collagen type I(${\alpha}$ 1), adducin gamma subunit, collagen type III(${\alpha}$ 1), fibronectin, lumican(keratan sulfate proteoglycan), and ${\alpha}$ -smooth muscle actin. Tissue inhibitor of metalloproteinase known as the enzyme controlling extracellular matrix with matrix metalloproteinase is more highly expressed in PDL cells, osteoprotegerin known as osteoclastogenesis inhibitory factor is more highly expressed in HGFs. We performed northern blot to verify cDNA microarray results on selected genes such as tissue inhibitor of metalloproteinase, fibronectin, osteoprogeterin. The result of northern blot analysis showed that each cell expressed the genes in similar pattern with cDNA microarray result. This result indicates that cDNA microarray is a reliable method in screening of gene expression profiles.

• Radiation Oncology Journal
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• 제37권1호
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• pp.37-42
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• 2019

Purpose: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. Results: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.