<로물루스 대제> 연구

송병욱 상명대학교 어문학연구소 1998 語文學硏究 Vol.8 No.-

Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-β1/Smad3 pathway

Byeong-Wook Song,Min-Ji Kim,Minji Kim,Hee Won Lee,Min Young Lee,Jongmin Kim,장우철 생화학분자생물학회 2020 BMB Reports Vol.53 No.11

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

Combination Therapy Comprising a Static Magnetic Field with Contractility Improves Skin Wounds

Song, Byeong-Wook,Hong, Hyunki,Jung, Yu Jin,Lee, Ju Hyung,Kim, Bong Soo,Lee, Hoon-Bum Mary Ann Liebert 2018 Tissue engineering. Part A Vol.24 No.17

<P>Cutaneous wounds can present significant clinical problems because of abnormal healing after deep dermal damage. Despite technical advances in wound care, there are still unmet needs that result from inefficient treatment. In this study, we aimed to improve skin wound healing using a contractibility band with static magnetic field (SMF), termed a magnetic band (Mb). To examine the effect of the Mb on wound healing, full-thickness 15x35mm excision wounds were surgically created on the dorsum of rats. An elastic and contractile band (nontreatment), or one neodymium magnet (Nd-1) or two magnets with an elastic and contractile band (Nd-2) were topically applied to the wound daily and the wound size was measured from day 1 to 7 after surgery. Nd-2 showed a significant (95%) reduction in the wound size on day 3. Histological analysis showed that proinflammatory cytokine levels were diminished by Nd-2, and granulation tissue and microvessels were increased compared with those in the sham group. During Mb-induced wound healing, apoptosis was significantly reduced and matrix remodeling-related factors were initially regulated. The results suggest that combination therapy comprising an SMF and an elastic and contractile band could be a promising tool to heal cutaneous wounds rapidly.</P>

Multiplexed targeting of microRNA in stem cell-derived extracellular vesicles for regenerative medicine

Byeong-Wook Song,Sekyung Oh,장우철 생화학분자생물학회 2022 BMB Reports Vol.55 No.2

Regenerative medicine is a research field that develops methodsto restore damaged cell or tissue function by regeneration, repairor replacement. Stem cells are the raw material of the bodythat is ultimately used from the point of view of regenerativemedicine, and stem cell therapy uses cells themselves or theirderivatives to promote responses to diseases and dysfunctions,the ultimate goal of regenerative medicine. Stem cell-derivedextracellular vesicles (EVs) are recognized as an attractive sourcebecause they can enrich exogenous microRNAs (miRNAs) bytargeting pathological recipient cells for disease therapy and canovercome the obstacles faced by current cell therapy agents. However, there are some limitations that need to be addressedbefore using miRNA-enriched EVs derived from stem cells formultiplexed therapeutic targeting in many diseases. Here, wereview various roles on miRNA-based stem cell EVs that caninduce effective and stable functional improvement of stemcell-derived EVs. In addition, we introduce and review the implicationsof several miRNA-enriched EV therapies improvedby multiplexed targeting in diseases involving the circulatorysystem and nervous system. This systemic review may offerpotential roles for stem cell-derived therapeutics with multiplexedtargeting.

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts

Song Byeong-Wook,Lee Chang Youn,Kim Ran,Kim Won Jung,Lee Hee Won,Lee Min Young,Kim Jongmin,Jeong Jee-Yeong,장우철 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a “multiplexed target” that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASC miR-210 ) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASC miR-210 ). Under hypoxic conditions, we observed that ASC miR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASC miR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASC miR-210 . These results suggest that the multiplexed target with ASC miR-210 is a useful tool for cardiovascular regeneration.

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

Song, Suk-Won,Chang, Woochul,Song, Byeong-Wook,Song, Heesang,Lim, Soyeon,Kim, Hye-Jung,Cha, Min-Ji,Choi, Eunju,Im, Sin-Hyeog,Chang, Byung-Chul,Chung, Namsik,Jang, Yangsoo,Hwang, Ki-Chul Wiley (John WileySons) 2009 Stem Cells Vol.27 No.6

<P>Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% +/- 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% +/- 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.</P>

A Combinational Therapy of Articular Cartilage Defects: Rapid and Effective Regeneration by Using Low-Intensity Focused Ultrasound After Adipose Tissue-Derived Stem Cell Transplantation

Song Byeong-Wook,Park Jun-Hee,Kim Bomi,Lee Seahyoung,Lim Soyeon,Kim Sang Woo,Choi Jung-Won,Lee Jiyun,Kang Misun,Hwang Ki-Chul,Chae Dong-Sik,Kim Il-Kwon 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.3

BACKGROUND: Although low-intensity pulsed ultrasound has been reported to be potential cartilage regeneration, there still unresolved treatment due to cartilage fibrosis and degeneration by a lack of rapid and high-efficiency treatment. The purpose of this study was to investigate the effect of a combination therapy of focused acoustic force and stem cells at site for fast and efficient healing on cartilage regeneration. METHODS: Using a rat articular cartilage defects model, one million adipose tissue-derived stem cells (ASCs) were injected into the defect site, and low-intensity focused ultrasound (LOFUS) in the range of 100–600 mV was used for 20 min/day for 2 weeks. All experimental groups were sacrificed after 4 weeks in total. The gross appearance score and hematoxylin and eosin (H&E), Alcian blue, and Safranin O staining were used for measuring the chondrogenic potential. The cartilage characteristics were observed, and type II collagen, Sox 9, aggrecan, and type X collagen were stained with immunofluorescence. The results of the comprehensive analysis were calculated using the Mankin scoring method. RESULTS: The gross appearance scores of regenerated cartilage and chondrocyte-like cells in H&E images were higher in LOFUS-treated groups compared to those in negative control or ASC-treated groups. Safranin O and Alcian blue staining demonstrated that the 100 and 300 mV LOFUS groups showed greater synthesis of glycosaminoglycan and proteoglycan. The ASC ? LOFUS 300 mV group showed positive regulation of type II collagen, Sox 9 and aggrecan and negative regulation of type X collagen, which indicated the occurrence of cartilage regeneration based on the Mankin score result. CONCLUSION: The combination therapy, which involved treatment with ASC and 300 mV LOFUS, quickly and effectively reduced articular cartilage defects.

Abies koreana 유래 정유의 항주름 및 미백 효과

송병욱(Byeong-Wook Song),송민정(Min-Jeong Song),박미진(Mi-Jin Park),최돈하(Don-Ha Choi),이성숙(Sung-Suk Lee),김명길(Myungkil Kim),황기철(Ki-Chul Hwang),김일권(Il-Kwon Kim) 한국생명과학회 2018 생명과학회지 Vol.28 No.5

구상나무로부터 추출된 정유가 개발되어 있지만, 피부와 연관된 연구 관점에서 효능이 아직까지 밝혀지지 않았다. 본 연구의 목적은 B16F10 흑색종 세포(B16F10)와 인간 피부아세포주(HDF)에서 멜라닌과 주름 형성 상의 구상나무 추출물 효과를 알아보는데 있다. 정유는 수첨 증류법으로 추출하였고 무수 황산나트륨으로 정제 하였다. 10<SUP>-5</SUP>배의 정유농도에서, 두 세포의 생존능은 세포독성 평가에 의해 확인 되었다. B18F10의 항멜라닌 효과는 티로시나아제 억제 분석과 티로시나아제, 티로시나아제 연관 단백질 -1과 -2(TRP-1, TRP-2)의 유전자 발현 검증을 통해 이루어졌다. 정유는 알파-멜라닌세포 자극 호르몬 유도 그룹과 비교하여 티로시나아제 억제 활성이 5배, 아르부틴 유도 그룹과 비교하였을 때 30% 정도 감소되었다. 3가지 멜라닌 유래 인자들의 mRNA 수준도 각각 증가하였다. 항주름 효과를 분석하기 위해, 프로콜라겐 타입 I c 펩티드 합성(PIP) 분석과 웨스턴 블록을 수행하였다. 정유를 처리한 그룹에서 PIP가 증가되었고 콜라겐 타입 1과 기질 금속 단백질 분해 효소가 개선 되었다. 또한 정유는 60 mJ/㎠의 자외선 조건에서, 자외선-억제 콜라겐 타입 1의 증가와 기질 금속 단백질 분해 효소 생성 억제를 통해 항주름 효과를 보여줬다. 따라서 구상나무 추출물은 미백과 항주름을 위한 안전하고 효과적인 피부 제재로서 가능성을 가지고 있음을 암시한다. The essential oil from Abies koreana E.H. Wilson had been developed, however, its efficacy has not yet been studied especially in terms of skin care research. The aim of this study is to investigate the effects of Abies koreana extracts (AKE) on melanogenesis and wrinkle formation in B16F10 melanoma cells (B16F10) and human dermal fibroblast cell line (HDF). The essential oil was extracted by hydrodistillation method and purified by anhydrous sodium sulfate. At a concentration of 10<SUP>-5</SUP>-fold, viability in these cells had been defined by cytotoxicity assays. Anti-melanogenic effects on B16F10 were evaluated using tyrosinase inhibition assay, and real-time PCR for verifying gene expression of tyrosinase, tyrosinase related protein-1 and -2 (TRP-1 and -2). AKEs reduced about 5-fold of tyrosinase inhibitory activity compared to α-melanocyte-stimulating hormone (α-MSH)-induced group and about 30% reduction compared to Arbutin induced group. The mRNA levels of three melanin-related factors were increased, separately. To investigate the effects of anti-wrinkle, procollagen type I c peptide synthesis assay (PIP) and Western blot were performed. At AKE-treated group, PIP was up-regulated and the expression of collagen type 1 and matrix metalloproteinase (MMP)-1 were improved. Furthermore, AKE presented anti-wrinkle effects by increasing UVB-inhibited collagen type 1 expression, and reducing UVB-induced MMP-1 production at 60 mJ/cm² of UVB radiation. Therefore, Abies koreana extracts has potentials as a safe and an effective skin ingredient for whitening and anti-wrinkle.

Safety and tolerability of Korean Red Ginseng in healthy adults: a multicenter, double-blind, randomized, placebo-controlled trial

Song, Sang-Wook,Kim, Ha-Na,Shim, Jae-Yong,Yoo, Byeong-Yeon,Kim, Dae-Hyun,Lee, Sang-Hyun,Park, Joo-Sung,Kim, Moon-Jong,Yoo, Jun-Hyun,Cho, BeLong,Kang, Hee-Cheol,Kim, Kwang-Min,Kim, Sung-Soo,Kim, Kyung- The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.4

Background: Korean Red Ginseng (KRG) has been used in Asia for its various biological effects, but no studies have investigated the safety of its long-term intake. Therefore, the present study evaluated the safety of KRG intake for 24 weeks. Methods: We randomized 1,000 participants in a 1:1 ratio into two groups, which were treated daily with 2 g of KRG or a placebo for 24 weeks. The primary endpoint was all adverse events and adverse drug reactions (ADRs) that occurred after KRG or placebo administration, which were reported at week 4, 12, and 24 after the baseline visit. Results: In total, 192 and 211 participants experienced adverse events in the KRG and placebo groups (39.2% and 42.0%, respectively; p = 0.361), and 59 and 57 KRG- and placebo-treated individuals reported ADRs (12.0% and 11.4%, respectively; p = 0.737). The frequently occurring ADRs were pruritus (2.0%), headache (1.6%), diarrhea (1.4%), and dizziness (1.2%) in the KRG group and pruritus (2.0%), headache (1.8%), dizziness (1.6%), rash (1.4%), and diarrhea (1.2%) in the placebo group. Discontinuation of drug administration due to ADRs was reported in 13 participants, six (1.2%) and seven (1.4%) in the KRG and placebo groups, respectively (p = 0.814). No significant abnormal changes were revealed by anthropometric, laboratory, and vital sign measurements in the KRG group compared with those in the placebo group. Conclusion: The present study confirms the safety and tolerability of daily intake of 2 g of KRG for 24 weeks by healthy adults.

Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study

( Byeong Wook Cho ),( Seok Bae Kim ),( Il Han Song ),( Sae Hwan Lee ),( Hong Soo Kim ),( Tae Hee Lee ),( Young Woo Kang ),( Seok Hyun Kim ),( Byung Seok Lee ),( Hee Bok Chae ) 대한간학회 2017 Clinical and Molecular Hepatology(대한간학회지) Vol.23 No.1

Background/Aims: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. Methods: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. Results: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. Conclusions: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon. (Clin Mol Hepatol 2017;23:51-56)