• Korean Journal of Pharmacognosy
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• v.43 no.1
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• pp.27-31
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• 2012

This study was designed to elucidate the effects of Cirsium japonicum (CJ) extracts on hepatic stellate cells (HSCs, LX-2 cells) proliferation, which is induced by platelet-derived growth factor (PDGF) or transforming growth factor-${\beta}$ (TGF-${\beta}$). The content of total phenol, flavonoid, and silymarin derivatives was more higher in CJ-flower than in CJ-root. Consistent with these results, the LX-2 cells growth inhibition was more effective in CJ-flower extract than in CJ-root extract, the complete growth inhibition concentration was $1{\mu}g/mL$ and $50{\mu}g/mL$, respectively. These results suggest that extracts from CJ-flower can be potentially used as therapeutic substances for the regulatioin of HSCs activation.

• Biomedical Science Letters
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• v.30 no.1
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• pp.10-16
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• 2024

Oxidative stress caused by elevated reactive oxygen species (ROS) in the heart causes various heart diseases. Oxidative stress is known as a factor that causes diseases in various organs as well as the heart. Diseases such as heart failure, myocardial infarction, and cardiomyopathy caused by oxidative stress in the heart can be treated with medication or surgery. Recently, blood cells concentrate (BCC) is used in various treatment areas such as orthopedics, gynecology, and urology. BCC therapy is applied to treatment by concentrating platelets and white blood cells necessary for regeneration through simple centrifugation using autologous blood. As the platelets are activated, many growth factors are released from alpha granules of the platelets. Growth factors such as TGF-β1, PDGF, VEGF, and EGF derived from platelets are involved in various cell signaling pathway. Due to these growth factors, BCC can contribute to tissue regeneration and can treat various diseases. CD34+ cells contained in BCC may also play an important role in tissue regeneration. In this study, we investigated whether BCC has a regenerative effect on heart disease, and if so, what mechanism causes the effect. To observe this, cardiomyocyte cells were treated with H₂O₂ to induce oxidative stress. And the effect was confirmed in the presence or absence of BCC. As a result, in the presence of BCC, the oxidative stress of cardiomyocyte cells was reduced and cell damage was also reduced. These results suggest that BCC therapy can be a new treatment alternative for heart disease.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.7
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• pp.1055-1059
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• 2003

Keratins, the constituents of epithelial intermediate filaments, are precisely regulated in a tissue and development specific manner. There are two types of keratin in bovine. The type I is acidic keratin and the type II is neutral/basic keratin. 1.5 kb of 5' flanking sequence of Korean cattle Keratin IV gene, type II keratin (59 kDa), was cloned and sequenced. A symmetrical motif AApuCCAAA are located in a defined region upstream of the TATA box. Proximal SP1, AP1, E-box and CACC elements as the major determinants of transcription are identified. When it was compared to the bovine sequence from -600 bp to ATG upstream, the homology was 97% in nucleotide sequence. Several A and T sequences, located in the promoter region, are deleted in the Korean cattle. An expression vector consisted of Korean cattle Keratin IV gene promoter/SV40 large T antigen was transfected to HaCaT cell (Epithelial keratinocyte). The transformed HaCaT cells showed active proliferation when treated with PDGF (Platelet-derived growth factor) in 0.3% soft agar compared to control cells. These results indicate that Korean cattle Keratin IVgene promoter can be used as a promoter for transfection into epithelial cell.

• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.407-417
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• 1995

In order to evaluate the effect of platelet-derived growth factor(PDGF-BB) and guided tissue regeneration(GTR) technique on the regeneration of destructed periodontal tissue,intentional through-and-through furcation defects(4mm in height) were made on both mandibular 2nd and 4th premolars of 8 adult male dogs(30-40lb). Experimental group 1 was composed of the premolars that were treated by only topical application of PDGF-BB with 0.05M acetic acid without any barrier membrane. Experimental group 2 was composed of the premolars that were treated by GTR with expanded polytetrafluoroethylene membrane(ePTFE : Gore-tex periodontal material, USA). Experimental group 3 was composed of the premolars that were treated by GTR with ePTFE after topical application of PDGFBE. Control group was composed of the premolars that were treated by coronally positioned flap operation only without use of PDGF-BB and ePTFE membrane. All ePTFE membranes were carefully removed 4 weeks after regenerative surgery, and all experimental animals were sacrificed 8 weeks after regenerative surgery. The light microscopic findings were as follows ; (1) In experimental group 1, rapid new bone formation along the-root surface with multiple ankylosis and root resorption by multinucleated giant cells, and dense connective tissue in the central portion of the furcation defects were observed. (2) In experimental group 2, it was observed that the furcation defects were filled with newly formed bone, Sharpey's fibers were embedded into new cementum on root dentin of furcation fornix area, but the central portion and the area under furcation fornix were still filled with dense connective tissue. (3) In experimental group 3, the furcation defects were regenerated with newly formed dense bone and regular periodontal ligament with Sharpey's fibers embedded into newly formed cementum and bone underneath fornix area. (4) In control group, unoccupied space, apical migration of epithelium, dense infiltration of inflammatory cells in subepithelial connective tissue in relation to heavy plaque accumulation, and root resorption by inflammatory reaction were shown, but any new cementum formation on resorbed dentin surface could not be observed. The present study demonstrated that the combined therapy of PDGF-BB and GTR could enhance the regeneration of destructed periodontal tissue.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.139-157
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• 2006

In the present study, I have investigated the bee venom (BV) and melittin (a major component of BV) -mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 50 ng/ml platelet derived growth factor BB (PDGF-BB)-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. I examined the effects on $NF-{\kappa}B$ activation to investigate a possible mechanism for anti-proliferative effects of BV and melittin, the PDGF-BB-induced $I{\kappa}B{\alpha}$ phosphorylation and its degradation were potently inhibited by melittin, and DNA binding activity and nuclear translocation of $NF-{\kappa}B$ p50 subunit in response to the action of PDGF-BB were potently attenuated by melittin. In further investigations, melittin markedly inhibited the PDGF-BB-induced phosphorylation of Akt but not ERK1/2, upstream signals of $NF-{\kappa}B$. Treatment of melittin also potently induced pro-apoptotic protein p53, Bax, and caspase-3 expression, but decreased anti-apoptotic protein Bcl-2 expression. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs through induction of apoptosis via suppressions of $NF-{\kappa}B$ and Akt activation, and enhancement of apoptotic signal pathway. Based on these results, BV acupuncture can be a candidate as a therapeutic method for restenosis and atherosclerosis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.349-360
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• 2018

Autophagy has been studied as a therapeutic strategy for cardiovascular diseases. However, insufficient studies have been reported concerning the influence of vascular smooth muscle cells (VSMCs) through autophagy regulation. The aim of the present study was to determine the effects of VSMCs on the regulation of autophagy under in vitro conditions similar to vascular status of the equipped micro-tubule target agent-eluting stent and increased release of platelet-derived growth factor-BB (PDGF-BB). Cell viability and proliferation were measured using MTT and cell counting assays. Immunofluorescence using an $anti-{\alpha}-tubulin$ antibody was performed to determine microtubule dynamic formation. Cell apoptosis was measured by cleavage of caspase-3 using western blot analysis, and by nuclear fragmentation using a fluorescence assay. Autophagy activity was assessed by microtubule-associated protein light chain 3-II (LC-II) using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured using $H_2DCFDA$. The proliferation and viability of VSMCs were inhibited by microtubule regulation. Additionally, microtubule-regulated and PDGF-BB-stimulated VSMCs increased the cleavage of caspase-3 more than only the microtubule-regulated condition, similar to that of LC3-II, implying autophagy. Inhibitory autophagy of microtubule-regulated and PDGF-BB-stimulated VSMCs resulted in low viability. However, enhancement of autophagy maintained survival through the reduction of ROS. These results suggest that the apoptosis of conditioned VSMCs is decreased by the blocking generation of ROS via the promotion of autophagy, and proliferation is also inhibited. Thus, promoting autophagy as a therapeutic target for vascular restenosis and atherosclerosis may be a good strategy.

• Journal of Biomedical Engineering Research
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• v.40 no.1
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• pp.1-6
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• 2019

Human mesenchymal stem cells (hMSC) are multipotent stromal cells that have great potential to differentiate into a variety of cell types such as osteocytes, chondrocytes, and myocytes. Although there have been many studies on their clinical availability, little is known about how intracellular signals can be modulated by topographic features of the extracellular matrix (ECM). In this study, we investigated whether and how microwavy-patterned extracellular matrix (ECM) could affect the signaling activity of focal adhesion kinase (FAK), a key cellular adhesion protein. The fluorescence resonance energy transfer (FRET)-based FAK biosensor-transfected cells are incubated on microwavy-patterned surfaces and then platelet derived growth factor (PDGF) are treated to trigger FAK signals, followed by monitoring through live-cell FRET imaging in real time. As a result, we report that PDGF-induced FAK was highly activated in cells cultured on microwavy-patterned surface with L or M type, while inhibited by H type-patterned surface. In further studies, PDGF-induced FAK signals are regulated by functional support of actin filaments, microtubules, myosin-related proteins, suggesting that PDGF-induced FAK signals in hMSC upon microwavy surfaces are dependent on cytoskeleton (CSK)-actomyosin networks. Thus, our findings not only provide new insight on molecular mechanisms on how FAK signals can be regulated by distinct topographical cues of the ECM, but also may offer advantages in potential applications for regenerative medicine and tissue engineering.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.338-345
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• 2002

Background : Coal workers' pneumoconiosis(CWP) is a fibrotic lung disease resulting from the chronic inhalation of coal dust. Various cytokines and growth factors secreted from macrophages and monocytes play a key role in the pathogenesis of pneumoconiosis. The platelet-derived growth factor (PDGF)-BB and the insulin-like growth factor(IGF)-1 secreated from the macrophages and monocytes are believed to stimulate the accumulation of mesenchymal cells and fibrosis of the lower respiratory tract that is observed in fibrotic lung disease. The serum concentraion of PDGF-BB and IGF-1 in 30 CWP patients and 10 healthy controls were measured in order to determine if PDGF-BB and IGF-1 can be used as sensitive biomarkers in CWP. Method : Serum was collected from 30 patients with CWP(13 with simple CWP and 17 with complicated CWP) and 10 healthy controls. The serum concentrations of PDGF-BB and IGF-1 were measured using ELISA (R&D system, Minneapolis, MN). Results : The serum PDGF-BB concentration in patients with complicated CWP($10083.76{\pm}639.07pg/mL$) was significantly higher than in the patients with simple CWP ($8493.88{\pm}848.51pg/mL$) and the healthy controls ($3726.17{\pm}292.20pg/mL$) (p<0.05). Compared to the healthy controls ($413.40{\pm}1.94ng/mL$), there was no significant difference in the serum IGF-1 concentration in patients with simple ($366.77{\pm}183.67ng/mL$) and complicated CWP ($403.18{\pm}15.39ng/mL$) (p>0.05). Conclusion : These results show the important role of the PDGF-BB mediated pathways in the pathogenesis of CWP. These data suggests that the PDGF-BB serum concentration is a useful biomarkers of the fibrotic extent in CWP patients.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.102.2-103
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• 2003

It has been previously reported that luteolin and luteolin-7-glucoside displayed the potent anti-oxidant and anti-inflammatory effects, which have also been successful in reducing vascular smooth muscle cells(VSMCs) proliferation. In this study, a possible anti-proliferative effect and its mechanism on rat aortic VSMCs by luteolin and luteolin-7-glucoside were investigated. Luteolin significantly inhibited the platelet-derived growth factor(PDGF)-BB-induced proliferation of rat aortic VSMCs. While luteolin-7-glucoside weakly inhibited the proliferation. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.182.2-182.2
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• 2003

The abnormal proliferation and migration of vascular smooth muscle cell (SMC) play an important role in the pathology of coronary artery atherosclerosis and restenosis. Platelet-derived growth factor (PDGF) is one of the most potent promoters of the proliferation and migration of the SMC. The heterocyclic quinones represent an important class of biologically active molecules. However, the inhibitory activity of quinone classes on the proliferation of the SMC has not been reported. (omitted)