Therapeutic exosomes for various human diseases: Special issue of BMB Reports in 2022

( Chulhee Choi ) 생화학분자생물학회 2022 BMB Reports Vol.55 No.1

Pirfenidone inhibits transforming growth factor-β1-induced fibrogenesis by blocking nuclear translocation of Smads in human retinal pigment epithelial cell line ARPE-19

Choi, Kyungsun,Lee, Kihwang,Ryu, Seung-Wook,Im, Minju,Kook, Koung Hoon,Choi, Chulhee Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>Transforming growth factor-β (TGF-β) plays a key role in transforming retinal pigment epithelial (RPE) cells into mesenchymal fibroblastic cells, which are implicated in proliferative vitreoretinopathy. Herein, we tested the effect of pirfenidone, a novel antifibrotic agent, on TGF-β1-mediated fibrogenesis in the human RPE cell line ARPE-19.</P><P><B>Methods</B></P><P>The effect of pirfenidone on the TGF-β1-induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. Fibronectin and collagen production was measured with enzyme-linked immunosorbent assay, and cell migration activity was investigated using a scratch assay. Immunoblot analyses of cofilin, sma and mad protein (smad) 2/3, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular signal-related kinase expression were conducted to elucidate the cell signaling networks that contribute to the antifibrotic effect of pirfenidone.</P><P><B>Results</B></P><P>Treatment with TGF-β1 induced typical phenotypic changes such as formation of stress fiber running parallel to the long axis of cells and enhanced migration and production of extracellular matrix components such as collagen type I and fibronectin. This fibroblast-like phenotype induced by TGF-β1 was significantly inhibited by pretreatment with pirfenidone in a dose-dependent manner. We also elucidated the TGF-β signaling pathways as the target of the inhibitory effect of pirfenidone. Pirfenidone inhibited TGF-β signaling by preventing nuclear accumulation of active Smad2/3 complexes rather than phosphorylation of Smad2/3.</P><P><B>Conclusions</B></P><P>These results collectively provide a rational background for future evaluation of pirfenidone as a potential antifibrotic agent for treating proliferative vitreoretinopathy and other fibrotic retinal disorders.</P>

Sheathless Focusing of Microbeads and Blood Cells Based on Hydrophoresis

Choi, Sungyoung,Song, Seungjeong,Choi, Chulhee,Park, Je-Kyun WILEY-VCH Verlag 2008 Small Vol.4 No.5

<P>This paper presents a microfluidic device for sheathless focusing of microbeads and blood cells based on a hydrophoretic platform comprising a V-shaped obstacle array (VOA). The VOA generates lateral pressure gradients that induce helical recirculations. Following the focusing flow particles passing through the VOA are focused in the center of the channel. In the device, the focusing pattern can be modulated by varying the gap height of the VOA. To achieve complete focusing within 4.4% coefficient of variation, the relative size differences between the gap and the particle were 3 and 4 µm for 10 and 15 µm beads, respectively. Red blood cells were used to study the hydrophoretic focusing pattern of biconcave, disk-shaped particles.</P> <B>Graphic Abstract</B> <P>A sheathless focusing method is developed based on a hydrophoretic platform comprising a V-shaped obstacle array (VOA). Hydrophoretic focusing of microparticles is performed along transverse pressure gradients and recirculation flows generated by the VOA. The schematic image shows the focusing pattern of a microparticle passing through the VOA with schematic streamlines. <img src='wiley_img/16136810-2008-4-5-SMLL200700308-content.gif' alt='wiley_img/16136810-2008-4-5-SMLL200700308-content'> </P>

Multiplex Analysis of Cytokines in the Serum and Cerebrospinal Fluid of Patients With Alzheimer's Disease by Color-Coded Bead Technology

Choi, Chulhee,Jeong, Jee-Hyang,Jang, Joong Sik,Choi, Kyungsun,Lee, Jungsul,Kwon, Jongbum,Choi, Kyoung-Gyu,Lee, Jong-Seo,Kang, Sang Won 대한신경과학회 2008 Journal of Clinical Neurology Vol.4 No.2

<P><B>Background and purpose</B></P><P>The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimer's disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests.</P><P><B>Methods</B></P><P>In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 <I>de novo</I> patients (13 controls, 11 AD, and 8 Parkinson's disease [PD]).</P><P><B>Results</B></P><P>MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group.</P><P><B>Conclusions</B></P><P>The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.</P>

Label-free optical control of arterial contraction.

Choi, Myunghwan,Yoon, Jonghee,Choi, Chulhee SPIE--the International Society for Optical Engine 2010 JOURNAL OF BIOMEDICAL OPTICS Vol.15 No.1

<P>The diameters of blood vessels, especially in the brain, change dynamically over time to provide sufficient blood supply as needed. No existing technique allows noninvasive control of vascular diameter in vivo. We report that label-free irradiation with a femtosecond pulsed laser can trigger blood vessel contraction in vivo. In response to laser irradiation, cultured vascular smooth muscle cells showed a rapid increase in calcium concentration, followed by cell contraction. In a murine thinned skull window model, laser irradiation focused in the arterial vessel wall caused localized vascular contraction, followed by recovery. The nonlinear nature of the pulsed laser allowed highly specific targeting of subcortical vessels without affecting the surrounding region. We believe that femtosecond pulsed laser irradiation will become a useful experimental tool in the field of vascular biology.</P>

Continuous blood cell separation by hydrophoretic filtration

Choi, Sungyoung,Song, Seungjeong,Choi, Chulhee,Park, Je-Kyun Royal Society of Chemistry 2007 Lab on a chip Vol.7 No.11

<P>We propose a new hydrophoretic method for continuous blood cell separation using a microfluidic device composed of slanted obstacles and filtration obstacles. The slanted obstacles have a larger height and gap than the particles in order to focus them to a sidewall by hydrophoresis. In the successive structure, the height and gap of the filtration obstacles with a filtration pore are set between the diameters of small and large particles, which defines the critical separation diameter. Accordingly, the particles smaller than the criterion freely pass through the gap and keep their focused position. In contrast, the particles larger than the criterion collide against the filtration obstacle and move into the filtration pore. The microfluidic device was characterized with polystyrene beads with a minimum diameter difference of 7.3%. We completely separated polystyrene microbeads of 9 and 12 µm diameter with a separation resolution of ∼6.2. This resolution is increased by 6.4-fold compared with our previous separation method based on hydrophoresis (S. Choi and J.-K. Park, <I>Lab Chip</I>, 2007, 7, 890, ref. 1). In the isolation of white blood cells (WBCs) from red blood cells (RBCs), the microfluidic device isolated WBCs with 210-fold enrichment within a short filtration time of ∼0.3 s. These results show that the device can be useful for the binary separation of a wide range of biological particles by size. The hydrophoretic filtration as a sample preparation unit offers potential for a power-free cell sorter to be integrated into disposable lab-on-a-chip devices.</P> <P>Graphic Abstract</P><P>This paper describes a novel hydrophoretic method for continuous blood cell separation using filtration obstacles, which play not only the role of filtering large particles blocked by the obstacles but also the role of focusing small particles able to pass through the gap between the obstacle and the top or bottom of the channel. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b705203k'> </P>

Label-free optical activation of astrocyte in vivo.

Choi, Myunghwan,Yoon, Jonghee,Ku, Taeyun,Choi, Kyungsun,Choi, Chulhee SPIE--the International Society for Optical Engine 2011 Journal of biomedical optics Vol.16 No.7

<P>As the most abundant cell type in the central nervous system, astrocyte has been one of main research topics in neuroscience. Although various tools have been developed, at present, there is no tool that allows noninvasive activation of astrocyte in vivo without genetic or pharmacological perturbation. Here we report a noninvasive label-free optical method for physiological astrocyte activation in vivo using a femtosecond pulsed laser. We showed the laser stimulation robustly induced astrocytic calcium activation in vivo and further verified physiological relevance of the calcium increase by demonstrating astrocyte mediated vasodilation in the brain. This novel optical method will facilitate noninvasive physiological study on astrocyte function.</P>

Restenosis after Angioplasty

Choi, Chulhee 이화여자대학교 세포신호전달연구센터 2003 고사리 세포신호전달 심포지움 Vol. No.5

By-pass surgery and percutaneous transluminal(coronary) angioplasty, PT(C)A, are standard techniques for the treatment of vascular occlusions. Their usefulness is limited by by-pass graft failure and restenosis occurring after the procedures. Twenty percent of patients treated with PTCA/PTA need a new revascularization procedure within 6 months, despite a successful procedure. Stents are used to prevent restenosis in selected lesions, but in-stent restenosis also remains an important clinical problem. The pathophysiology of restenosis involves early elements of direct injury to smooth muscle cells, deendothelialization, and thrombus deposition. This leads to smooth muscle cell proliferation/migration and extracellular matrix deposition. There is an increasing body of evidence to suggest that inflammation plays a pivotal role linking early vascular injury to the eventual consequence of neointimal growth and lumen compromise. The widespread use of coronary/carotid stents has fundamentally altered the vascular response to injury by causing a more intense and prolonged inflammatory state.

Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II

Choi, Min Hee,Lee, In Kyung,Kim, Gyung Whan,Kim, Bang Ul,Han, Ying-Hao,Yu, Dae-Yeul,Park, Hye Sun,Kim, Kyung Yong,Lee, Jong Seo,Choi, Chulhee,Bae, Yun Soo,Lee, Byung In,Rhee, Sue Goo,Kang, Sang Won Nature Publishing Group 2005 Nature Vol.435 No.7040

Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H<SUB>2</SUB>O<SUB>2</SUB> (refs 1, 2–3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H<SUB>2</SUB>O<SUB>2</SUB> produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H<SUB>2</SUB>O<SUB>2</SUB>, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cγ1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H<SUB>2</SUB>O<SUB>2</SUB> in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease.

핸드오버 우선순위를 고려한 이동성 인식 호 수락제어 알고리즘

최철희(ChulHee Choi),조동호(Dong-Ho Cho) 한국통신학회 2014 한국통신학회 학술대회논문집 Vol.2014 No.6