• 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.

• BMB Reports
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• v.57 no.4
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• pp.200-205
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• 2024

We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohisto-chemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosis-related signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures.

• The Korean Journal of Physiology and Pharmacology
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• v.71 no.1
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• pp.155-165
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• 2020

Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.

• Journal of Biomedical Engineering Research
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• v.27 no.6
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• pp.418-426
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• 2006

In the artificial heart application, productivity and hemodynamic properties of artificial heart valves are crucial in successiful application to long term in vivo trials. This paper is about manufacture and assessment of trileaflet polymer heart valves using vacuum forming process(VFP). The VFP has many advantages such as reduced fabrication time, reproducibility due to relatively easy and simple process for manufacturing. Prior to VFP of trileaflet polymer heart valves, polyurethane(Pellethane 2363 80AE, Dow Chemical) sheet was prepared by extrusion. The sheets were heated and formed to mold shape by vacuum pressure. The vacuum formed trileaflet polymer heart valves fabrication is composed of two step method, first, leaflet forming and second, conduit forming. This two-step forming process made the leaflet-conduit bonding stable with any organic solvents. Hydrodynamic properties and hemocompatibility of the vacuum formed trileaflet polymer heart valves was compared with sorin bicarbon bileaflet heart valve. The percent effective orifice area of vacuum formed trileaflet polymer heart valves was inferior to bileaflet heart valve, but the increase of plasma free hemoglobin level which reflect blood damage was superior in vacuum formed trileaflet polymer heart valves Vacuum formed trileaflet polymer heart valves has high productivity, and superior hemodynamic property than bileaflet heart valves. Low manufacturing cost and blood compatible trileaflet polymer heart valves shows the advantages of vacuum forming process, and these results give feasibility in in vivo animal trials in near future, and the clinical artificial heart development program.

• Investigative Magnetic Resonance Imaging
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• v.17 no.3
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• pp.169-180
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• 2013

Purpose : The purpose of this study was to setup a concuurent transcranial magnetic stimulation (TMS)-functional MRI (fMRI) system for understanding causality of the functional brain network. Materials and Methods: We manufactured a TMS coil holder using nonmagnetic polyether ether ketone (PEEK). We simulated magnetic field distributions in the MR scanner according to TMS coil positions and angles. To minimize image distortions caused by TMS application, we controlled fMRI acquisition and TMS sequences to trigger TMS during inter-volume intervals. Results: Simulation showed that the magnetic field below the center of the coil was dramatically decreased with distance. Through the MR phantom study, we confirmed that TMS application around inter-volume acquisition time = 100 miliseconds reduced imaging distortion. Finally, the applicability of the concurrent TMS-fMRI was tested in preliminary studies with a healthy subject conducting a motor task within TMS-fMRI and passive motor movement induced by TMS in fMRI. Conclusion: In this study, we confirmed that the developed system allows use of TMS inside an fMRI system, which would contribute to the research of brain activation changes and causality in brain connectivity.

• IE interfaces
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• v.14 no.4
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• pp.429-440
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• 2001

Brain Korea(BK) 21 is a plan launched in 2000 to strengthen the competitiveness of research and education quality of universities in Korea. In this paper, we evaluate BK21 plan using both ACSI and SEM in terms of the satisfaction level of graduate students in various dimension. The results of our study indicate that in general BK21 has a significant impact on the satisfaction of the graduate students involved in BK21. It turns out that the scholarship is the only one component which is positively related to the students' satisfaction while the industry-university cooperation system and the international conference attendance and Journal publication have negative relationship with satisfaction. In addition, it appears that those who graduated from other college and participate in BK21 tend to be more satisfied than those who admitted to the graduate program from the same college. Our study results imply that some strategies for BK21 need to be modified and effectively implemented in order to increase the number of applicant of good quality and level up the satisfaction level of the graduate students in Korea.

• Biomedical Science Letters
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• v.10 no.4
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• pp.385-389
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• 2004

A novel gene Jpk, originally isolated as a trans-acting factor associating with the position-specific regulatory element of murine Hox gene has been reported to be expressed differentially in the liver of diabetic animals. Therefore, in an attempt to develop a possible diagnostic marker and/or new therapeutic agent for the Diabetes Mellitus, we analysed the expression pattern of Jpk among organs of normal and diabetic Sprague-Dawley (SD) rats. Total RNAs were isolated from each organs (brain, lung, heart, liver, spleen, kidney, muscle, blood, and testis) of diabetic and normal rats in both normal feeding and after fasting condition. And then RT (reverse transcription) PCR has been performed using Jpk­specific primers. The Jpk gene turned out to be expressed in all organs tested, with some different expression profiles among normal and diabetes, though. Upon fasting, Jpk expressions were reduced in all organs tested except kidney, muscle and brain of normal rat. Whereas in diabetes, Jpk expressions were increased in all organs except heart, muscle and testis when fasted. Compared to the normal rat, the Jpk expression level in blood was remarkably upregulated (about 15-30times) in diabetic rat whether in normal feeding or fasting conditon, suggesting that the Jpk could be a candidate gene for the possible blood diagnostic marker for the Diabetes Mellitus.

• Molecules and Cells
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• v.26 no.6
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• pp.566-575
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• 2008

Twenty-five chipmunk species occur in the world, of which only the Siberian chipmunk, Tamias sibiricus, inhabits Asia. To investigate mitochondrial cytochrome b sequence variations and population structure of the Siberian chipmunk in northeastern Asia, we examined mitochondrial cytochrome b sequences (1140 bp) from 3 countries. Analyses of 41 individuals from South Korea and 33 individuals from Russia and northeast China resulted in 37 haplotypes and 27 haplotypes, respectively. There were no shared haplotypes between South Korea and Russia - northeast China. Phylogenetic trees and network analysis showed 2 major maternal lineages for haplotypes, referred to as the S and R lineages. Haplotype grouping in each cluster was nearly coincident with its geographic affinity. In particular, 3 distinct groups were found that mostly clustered in the northern, central and southern parts of South Korea. Nucleotide diversity of the S lineage was twice that of lineage R. The divergence between S and R lineages was estimated to be 2.98-0.98 Myr. During the ice age, there may have been at least 2 refuges in South Korea and Russia - northeast China. The sequence variation between the S and R lineages was 11.3% (K2P), which is indicative of specific recognition in rodents. These results suggest that T. sibiricus from South Korea could be considered a separate species. However, additional information, such as details of distribution, nuclear genes data or morphology, is required to strengthen this hypothesis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.3
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• pp.283-291
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• 2008

The malar mound defines the contour of the lateral face between the inferior orbital rim and the mandible, and hypoplasia or asymmetry of this region is readily noticeable. A flat, hypoplastic malar eminence can make the face blunt and wearisome, which contributes to a premature aged appearance. Patients with congenital or traumatic flattening of the malar eminence can obtain esthetic improvement with implants. Indications for placement of malar implants to improve the appearance of subtle flattening or to enhance the esthetic harmony of a patient's face have been suggested in several studies. Many augmentation materials, such as silicone, proplast, polyamide, and porous polyethylene implants have been used. Many methods of localization have been described, the key to proper placement of the implants lies in a through understanding of the esthetics of the malar mound. From August 2001 to June 2007, 12 patients with malar depression who visited the Department of Oral and Maxillofacial Surgery, Chonnam National University Hospital were treated by augmentation malarplasty with Porous polyethylene. The location and amount of augmentation are determined by preoperative interview, physical examinations, facial models and radiographic findings. 12 patients were satisfied with the results of augmentation malarplasty and severe complications were not occurred.

• Animal cells and systems
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• v.15 no.4
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• pp.268-273
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• 2011

Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.