• Journal of Life Science
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• v.21 no.2
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• pp.286-291
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• 2011

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.504-518
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

• Journal of the Korean Society for Precision Engineering
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• v.32 no.8
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• pp.755-760
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• 2015

For proper wound healing, dermal contraction and remodeling are critical; during the natural healing process, differentiated fibroblasts called "myofibroblasts" typically undertake these functions. For severe wounds, however, a critical mass of dermal matrix and fibroblasts are lost, making self-regeneration impossible. To overcome this impairment, synthetic wound patches with embedded functional cells can be used to promote healing. In this study, we developed a polydioxanone (PDO)-based cell-embedded sheet on which dermal fibroblasts were cultured and induced for differentiation into myofibroblasts, whereby the following combinatorial physicochemical stimuli were also applied: aligned topology, electric field (EF), and growth factor. The results show that both the aligned topology and EF synergistically enhanced the expression of alpha smooth-muscle actin (${\alpha}$-SMA), a key myofibroblast marker. Our proof-of-concept (POC) experiments demonstrated the potential applicability of a myofibroblast-embedded PDO sheet as a wound patch.

• Natural Product Sciences
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• v.20 no.4
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• pp.262-268
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• 2014

Rutaecarpine is one of the major alkaloids present in the fruits of Evodia rutaecarpa. In this study, rutaecarpine was evaluated, both in vitro and in vivo, for its hepatoprotective properties against thioacetamide (TAA)-induced hepatic fibrosis. The results showed that rutaecarpine inhibited TAA-induced cytotoxicity, reduced the expression of the fibrogenic cytokine transforming growth factor ${\beta}1$ ($TGF-{\beta}1$), and induced the expression of bcl-2. To evaluate its in vivo effects, animal models with TAA-induced hepatic fibrosis were utilized. Levels of liver tissue injury-associated enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were monitored. $TGF-{\beta}1$ and the ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) were measured as markers of the protective effects on hepatic fibrosis. The AST and ALT levels in blood were greatly enhanced by TAA and completely blunted by rutaecarpine. Rutaecarpine led to the down-regulation of $TGF-{\beta}$ and Bax mRNA expression, as well as the up-regulation of Bcl-2 and $Bcl-X_L$ mRNA levels. In conclusion, rutaecarpine inhibited TAA-induced hepatic fibrosis and apoptosis by inducing the expression of Bcl-2 while blocking $TGF-{\beta}1$ in our TAA-intoxicated model.

• Journal of the Institute of Electronics and Information Engineers
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• v.49 no.10
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• pp.169-177
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• 2012

A non-decimation second-order spatial moving average (SMA) discrete-time (DT) filter is proposed with reconfigurable null frequencies. The filter coefficients are changeable, and it can be controlled by switching sampling capacitors. So, interferers can be rejected effectively by flexible nulls. Since it operates without decimation, it does not change the sample rate and aliasing problem can be avoided. The filter is designed with variable weight of coefficients as $1:{\alpha}:1$ where ${\alpha}$ varies from 1 to 2. This corresponds to the change of null frequencies within the range of fs/3~fs/2 and fs/2~2fs/3. The proposed filter is implemented in the TSMC 0.18-${\mu}m$ CMOS process. Simulation shows that null frequencies are changeable in the range of 0.38~0.49fs and 0.51~0.62fs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3307-3312
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• 2015

The papillary patterned lesion of thyroid may be challenging with many diagnostic pitfalls. Tumor stroma plays an important part in the determination of the tumor phenotype. CD34 is thought to be involved in the modulation of cell adhesion and signal transduction as CD34(+) fibrocytes are potent antigen-presenting cells. Smooth muscle actin (SMA) positivity could be diagnostic for fibroblast activation during tumorigenesis. We aimed to examine the expression of CD34 and alphaSMA in the stroma of papillary thyroid hyperplasia, papillary thyroid carcinoma and papillary tumors of uncertain malignant potential in order to elucidate their possible differential distribution and roles. A total number of 54 cases with papillary thyroid lesions were studied by routine H&E staining, CD34 and ASMA immunostaining. ASMA was not expressed in benign papillary hyperplastic lesions while it was expressed in papillary carcinoma, indicating that tumors have modulated stroma. Although the stroma was not well developed in papillary lesions with equivocal features of uncertain potentiality, CD34 was notable in such cases with higher incidence in malignant cases. So ASMA as well as CD34 could predict neoplastic behavior, pointing to the importance of the stromal role. Differences between groups suggest that the presence of CD34 + stromal cells is an early event in carcinogensis and is associated with neoplasia, however ASMA+ cells are more likely to be associated with malignant behavior and metastatic potential adding additional tools to the light microscopic picture helping in diagnosis of problematic cases with H&E.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.543-551
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• 2021

Nocardiopsis species produce bioactive compounds, such as antimicrobial and anti-cancer agents and toxins. However, no reports have described their anti-inflammatory and anti-fibrotic effects during nasal polyp (NP) formation. In this study, we investigated whether marine-derived bacterial Nocardiopsis sp. 13G027 exerts anti-inflammatory and anti-fibrotic effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and transforming growth factor (TGF)-β1-induced NP-derived fibroblasts (NPDFs). Nitric oxide (NO) and prostaglandin E₂ (PGE₂) levels were analyzed. Extract from Nocardiopsis sp. 13G027 significantly inhibited the upregulation of NO and PGE₂ in LPS-activated RAW 264.7 macrophages. The expression of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt/PKB) in LPS-induced RAW 264.7 macrophages was evaluated; smooth muscle alpha-actin (α-SMA), collagen type I (Col-1), and fibronectin also phosphorylated small mothers against decapentaplegic (SMAD) 2 and 3 in TGF-β1-stimulated NPDFs. The Nocardiopsis sp. 13G027 extract suppressed the phosphorylation of MAPKs and Akt and the DNA-binding activity of activator protein 1 (AP-1). The expression of pro-fibrotic components such as α-SMA, Col-1, fibronectin, and SMAD2/3 was inhibited in TGF-β1-exposed NPDFs. These findings suggest that Nocardiopsis sp. 13G027 has the potential to treat inflammatory disorders, such as NP formation.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.292-298
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• 2023

Objective: Ovarian torsion is a gynecological disorder that causes ischemia-reperfusion injuries in the ovary. Our study investigated berberine's short- and long-term effects on ovarian ischemia-reperfusion injuries. Methods: This study included 28 Wistar albino female rats weighing 180 to 220 g, which were divided into four groups: sham (S), torsion/detorsion (T/D), torsion/ detorsion+single dose berberine (T/D+Bb), and torsion/detorsion+15 days berberine (T/D+15Bb). The torsion and detorsion model was applied in all non-sham groups. In the T/D+Bb group, a single dose of berberine was administered, while in the T/D+15Bb group, berberine was administered over a period of 15 days. After the rats were euthanized, their ovaries were excised. The left ovaries were used for histopathologic evaluation, which included ovarian injury scoring and follicle count, while the right ovaries were used for biochemical analyses (tissue transforming growth factor-β [TGF-β] and alpha-smooth muscle actin [α-SMA] levels). Results: The histopathologic evaluation scores for the ovaries were significantly lower in the T/D+B group (p<0.05) and the T/D+15B group (p<0.005) than in the T/D group. The follicle counts in the T/D group were lower than those in both the sham and treated groups (p<0.005). The TGF-β levels were significantly lower in the T/D+15B group (p<0.005), whereas the α-SMA levels did not show a significant difference. Conclusion: Both short- and long-term berberine use could potentially have therapeutic effects on ovarian torsion. Long-term berberine use exhibited anti-inflammatory effects by reducing TGF-β levels, thereby preventing ischemia-reperfusion injuries. Therefore, we suggest that long-term berberine use could be beneficial for ovarian torsion.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.16-16
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• 2003

Hepatic fibrosis is a common response to various chronic hepatic injuries and occurs as a consequence of the transformation of hepatic stellate cells into myofibroblasts (MFBs) producing abnormal extracellular matrix which is mainly induced by transforming growth factor-beta (TGF-${\beta}$), especially TGF-${\beta}$1 [1,2]. As the liver becomes fibrotic, there are both quantitative and qualitative changes in several pathological markers related to the hepatic fibrosis. These fibrotic markers in liver are mainly consisted of several proteins and cytokines, but sometimes included specific type cells. The aim of this study was to detect expression and change of markers (TGF-${\beta}$, mallory body, cytokeratin, ${\alpha}$-SMA, hypoxia, collagen) during hepatic fibrogenesis. (omitted)