• Biomolecules & Therapeutics
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• v.30 no.2
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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.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.167-177
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• 2003

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.175-176
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• 2002

Airway inflammation is a characteristic of many lung disorders including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. All these diseases involve the recruitment of immune and inflammatory cells to the lungs leading to systemic and local chronic inflammation and oxidative stress. (omitted)

• Radiation Oncology Journal
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• v.12 no.2
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• pp.143-150
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• 1994

The damage which radiation produces in tissues such as the lungs can be discussed at the molecular, biophysical, cellular, and organ levels. The cellular effects of irradiating the lungs are related to the histologic and clinical sequelae. In the present study the right lung of rabbits were exposed to single dose of 20 Gy of X-irradiation. Animals from each group were sacrificed monthly for 6 months postexposure. Sections of lung were examined by light microscopy(LM) and by transmission electron microscopy(TEM). Multiple exudative lesions were seen at 2 months after the 20Gy irradiation,and they progressed to a proliferative and then reparative fibrotic lesion by 6 months. Changes in epithelial lining of lung components, particulary the presence of type II pneumocytes were found by both LM and TEM. Capillary endothelial damages were less pronounced. The possible implication of cellular components in radiation pneumonitis and fibrosis is discussed.

• Toxicological Research
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• v.20 no.1
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• pp.55-61
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• 2004

Respiratory effects in full time welders include bronchitis, airway irritation, lung function changes, and lung fibrosis. Welder's pneumoconiosis has been generally determined to be benign and not associated with respiratory symptoms based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Accordingly, to investigate pulmonary function changes during 60 days induced by welding-fume exposure, male Sprague-Dawley rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with concentrations of 64.8$\pm$0.9 mg/$m^3$ (low dose) and 107.8 $\pm$ 2.6 mg/$m^3$ (high dose) total suspended particulates for 2 hr/day, 5 days/week in an inhalation chamber for 60 days. Pulmonary function was measured every week with whole body plethysmograph compensated (WBP Comp, SFT38116, Buxco Electronics, Sharon, CT). The rats exposed to the high dose of welding fumes exhibited statistically significant (p<0.05~0.01) body weight decrease as compared to the control whereas cell number increase of the bronchoalveolar lavage fluid (BALF) (total cell, macrophage, polymorphonuclear cell and lymphocyte) during the 60 days exposure period. And only tidal volume was significantly decreased in dosedependantly during 60 days of MMA-SS welding fume exposure. This pulmonary function change with inflammatory cell recruitment confirms the lung injury caused by the MMA-SS welding fume exposure.

• Journal of the Korean Society of Radiology
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• v.83 no.5
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• pp.1175-1181
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• 2022

Progressive massive fibrosis (PMF) with atypical findings is often misdiagnosed as lung cancer. Atypical features of PMF have been described in some reports; however, these reports only introduced their cases with a short literature review. We report two cases of solitary PMFs with no underlying simple pneumoconiosis or rapid growth at atypical location that were mistaken for lung cancer. We also suggest the useful CT findings to aid in the differential diagnosis.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.81-85
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• 1991

The differentiation between post-radiotherapy lung fibrosis and tumor recurrence is often a dilemma to physicians. Twenty two patients with lung cancer who had received 45~60 Gy to the chest were chosen to study the possible role of gallium-67 scan. Seventeen squamous cell carcinomas were treated with only radiotherapy, 3 small cell carcinomas with combination chemotherapy, 2 adenocarcinomas with lobectomy. A total of 8 patients with pneumonitis with or without fibrosis and recurrence showed uptake of gallium at the site of inflammation. Of the 12 recurrences and residual diseases after radiotherapy, positive gallium uptake was present in 11 cases (92%). Of the 10 recurrence-free cases, all the 5 patients with pneumonitis revealed gallium accumulation. However, 4 of the 5 patients (80%) with recurrence-free fibrosis have not accumulated gallium in the fibrotic areas. Fibroses in S patients were developed after 8 months of completion of radiotherapy. These facts suggest that gallium-67 scan after 1 year post-treatment may aid for the discrimination of fibrosis from tumor recurrence unless pneumonitis is present.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2021.05a
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• pp.144-146
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• 2021

Idiopathic pulmonary fibrosis (IPF) is one of the most dreadful lung diseases which effects the performance of the lung unpredictably. There is no any authentic natural history discovered yet pertaining to this disease and it has been very difficult for the physicians to diagnosis this disease. With the advent of Artificial intelligent and its related technologies this task has become a little bit easier. The aim of this paper is to develop and to explore the machine learning models for the prediction and diagnosis of this mysterious disease. For our study, we got IPF dataset from Haeundae Paik hospital consisting of 2425 patients. This dataset consists of 502 features. We applied different data preprocessing techniques for data cleaning while making the data fit for the machine learning implementation. After the preprocessing of the data, 18 features were selected for the experiment. In our experiment, we used different machine learning classifiers i.e., Multilayer perceptron (MLP), Support vector machine (SVM), and Random forest (RF). we compared the performance of each classifier. The experimental results showed that MLP outperformed all other compared models with 91.24% accuracy.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.2
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• pp.108-113
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• 2020

Objective: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-β)-induced endometrial fibrosis. Methods: The efficacy of eupatilin on TGF-β-induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction. Results: Eupatilin treatment significantly reduced the fibrotic activity of TGF-β-induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-β-induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-β pretreatment and recovered to the levels of control cells in response to eupatilin treatment. Conclusion: Our findings suggest that suppression of TGF-β-induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.