Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for pluripotency and self-renewal of mouse embryonic stem cells via downregulation of Nanog transcription

( Songhwa Kang ),( Jisoo Yun ),( Da Yeon Kim ),( Seok Yun Jung ),( Yeon Ju Kim ),( Ji Hye Park ),( Seung Taek Ji ),( Woong Bi Jang ),( Jongseong Ha ),( Jae Ho Kim ),( Sang Hong Baek ),( Sang-mo Kwon ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.2

B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the NF-κB family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity. [BMB Reports 2018; 51(2): 92-97]

한국어 학습자 구어 자료 전사에서의 쟁점과 구어 전사의 실제

강현화(Kang Hyounhwa),한송화(Han Songhwa) 한국사전학회 2016 한국사전학 Vol.- No.27

The purpose of this paper is to address issues regarding verbal transcription in terms of peculiarities of learners’ spoken data, reliability between transcribers, issues of objective tagging and three aspects of efficiency and systemicity in corpus construction(transcription level, transcription limit and transcription method) building a computer-based learners’ corpus. First, considering the characteristics of the learners’ spoken language featuring inter-transfer as well as intra-transfer going beyond native speakers’ oral characteristics, there are a variety of the transcription level, transcription limit and transcription methods according to the purpose of utilization of learners’ spoken data. Second, in terms of tagging that increases the reliability and objectivity among transcribers, a focus will be put on the minimum guidelines needed for implementation of research objectives and program utilization ,subsequent simple transcription, training and step-by-step review. Third, issues of efficiency and systemicity are linked to the issue of efficiency and readability of the search and are associated with costs of economic feasibility. The simplistic processing of foreign LINDSEI can be referred to in this regard.

Safety and Effectiveness of Desvenlafaxine in Korean Patients with Major Depressive Disorder: A 6-month Postmarketing Surveillance Study

Sungwon Roh,Kang Soo Lee,Songhwa Choi,Jae-Min Kim 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.3

Objective: Although the safety and efficacy of desvenlafaxine have been demonstrated, long-term evidence in Asians is lacking. We examined the safety and effectiveness of desvenlafaxine for up to 6 months in routine clinical practice in Korea. Methods: This multicenter, open-label, prospective observational study was conducted from February 2014 to February 2020 as a postmarketing surveillance study of desvenlafaxine (ClinicalTrials.gov identifier: NCT02548949). Adult patients with major depressive disorder (MDD) were observed from the initiation of treatment for 8 weeks (acute treatment phase) and then up to 6 months (continuation treatment phase) in a subsample. Safety was evaluated by incidence of adverse events (AE) and adverse drug reactions. Treatment response was assessed using the Clinical Global ImpressionImprovement (CGI-I) scale. Results: We included 700 and 236 study subjects in the analysis of acute and continuation treatment phase, respectively. In acute treatment phase, AE incidence was 9.86%, with nausea being most common (2.00%). In continuation treatment phase, AE incidence was 2.97%, with tremor occurring most frequently. After acute treatment (n = 464), the treatment response rate according to the CGI-I score at week 8 was 28.9%. In long-term users (n = 213), the response rate at month 6 was 45.5%. During the study period, no clinically relevant changes in BP were found regardless of concomitant use of antihypertensive drugs. Conclusion: This study provides evidence on the safety and effectiveness of desvenlafaxine in adults with MDD, with a low incidence of AE, consistent AE profile with previous studies, and improved response after long-term treatment.

Engineered M13 Peptide Carrier Promotes Angiogenic Potential of Patient-Derived Human Cardiac Progenitor Cells and In Vivo Engraftment

장웅비,지승택,박지혜,Kim Yeon-Ju,Kang Songhwa,김다연,이나경,김진수,Lim Hye Ji,최재우,LE THI HONG VAN,LY THANH TRUONG GIANG,비누스,김동환,하종성,윤지수,Baek Sang Hong,권상모 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.3

BACKGROUND: Despite promising advances in stem cell-based therapy, the treatment of ischemic cardiovascular diseases remains a big challenge due to both the insufficient in vivo viability of transplanted cells and poor angiogenic potential of stem cells. The goal of this study was to develop therapeutic human cardiac progenitor cells (hCPCs) for ischemic cardiovascular diseases with a novel M13 peptide carrier. METHOD: In this study, an engineered M13 peptide carrier was successfully generated using a QuikChange Kit. The cellular function of M13 peptide carrier-treated hCPCs was assessed using a tube formation assay and scratch wound healing assay. The in vivo engraftment and cell survival bioactivities of transplanted cells were demonstrated by immunohistochemistry after hCPC transplantation into a myocardial infarction animal model. RESULTS: The engineered M13RGD?SDKP peptide carrier, which expressed RGD peptide on PIII site and SDKP peptide on PVIII site, did not affect morphologic change and proliferation ability in hCPCs. In contrast, hCPCs treated with M13RGD?SDKP showed enhanced angiogenic capacity, including tube formation and migration capacity. Moreover, transplanted hCPCs with M13RGD?SDKP were engrafted into the ischemic region and promoted in vivo cell survival. CONCLUSION: Our present data provides a promising protocol for CPC-based cell therapy via short-term cell priming of hCPCs with engineered M13RGD?SDKP before cell transplantation for treatment of cardiovascular disease.

A Role for Arabidopsis miR399f in Salt, Drought, and ABA Signaling

Baek, Dongwon,Chun, Hyun Jin,Kang, Songhwa,Shin, Gilok,Park, Su Jung,Hong, Hyewon,Kim, Chanmin,Kim, Doh Hoon,Lee, Sang Yeol,Kim, Min Chul,Yun, Dae-Jin Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.2

MiR399f plays a crucial role in maintaining phosphate homeostasis in Arabidopsis thaliana. Under phosphate starvation conditions, AtMYB2, which plays a role in plant salt and drought stress responses, directly regulates the expression of miR399f. In this study, we found that miR399f also participates in plant responses to abscisic acid (ABA), and to abiotic stresses including salt and drought. Salt and ABA treatment induced the expression of miR399f, as confirmed by histochemical analysis of promoter-GUS fusions. Transgenic Arabidopsis plants overexpressing miR399f (miR399f-OE) exhibited enhanced tolerance to salt stress and exogenous ABA, but hypersensitivity to drought. Our in silico analysis identified ABF3 and CSP41b as putative target genes of miR399f, and expression analysis revealed that mRNA levels of ABF3 and CSP41b decreased remarkably in miR399f-OE plants under salt stress and in response to treatment with ABA. Moreover, we showed that activation of stress-responsive gene expression in response to salt stress and ABA treatment was impaired in miR399f-OE plants. Thus, these results suggested that in addition to phosphate starvation signaling, miR399f might also modulates plant responses to salt, ABA, and drought, by regulating the expression of newly discovered target genes such as ABF3 and CSP41b.

Laser-irradiated inclined metal nanocolumns for selective, scalable, and room-temperature synthesis of plasmonic isotropic nanospheres

Noh, Myoung-Sub,Han, Soo Deok,Chae, Songhwa,Back, Seung Hyuk,Kim, Sangtae,Baek, Seung-Hyub,Kim, Seong Keun,Choi, Ji-Won,Kim, Jin-Sang,Ahn, Dong June,Choi, Dukhyun,Kang, Chong-Yun The Royal Society of Chemistry 2018 Journal of materials chemistry. C, Materials for o Vol.6 No.22

<P>Plasmonic nanocrystals, which exhibit extraordinary optical properties, are challenging to grow in selective positions with a cost-effective and high-throughput process. We demonstrate that plasmonic isotropic gold nanospheres (AuNSs) can be selectively synthesized on wafer-scale rigid and flexible substrates at room temperature by laser irradiation. First, we prepare gold nanocolumn (AuNC) thin films on sapphire and polydimethylsiloxane substrates with glancing angle deposition (GAD). Then, a KrF excimer laser is exposed at selected positions with a 24 ns pulse duration. Finally, highly isotropic AuNSs as plasmonic nanocrystals are synthesized at the targeted positions. We suggest that the formation of such isotropic AuNSs is caused by reshaping from the top of the AuNCs; this is verified by the temperature distribution in the AuNCs during laser irradiation through finite element method simulations. We further investigate the formation of AuNSs by varying the laser energy density and the kind of substrate. By using a simple mask process, we demonstrate patterning of the letters “KIST” <I>via</I> selectively grown AuNSs on a flexible substrate. The simple laser irradiation process on GAD-grown metal NC thin films is expected to be a promising method for scalable synthesis of plasmonic isotropic NSs at targeted positions with a rapid process and at room temperature.</P>

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

Da Yeon Kim,Seok Yun Jung,Yeon Ju Kim,Songhwa Kang,Ji Hye Park,Seung Taek Ji,Woong Bi Jang,Shreekrishna Lamichane,Babita Dahal Lamichane,Young Chan Chae,Dongjun Lee,Joo Seop Chung,Sang-Mo Kwon 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxiainduced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia timedependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

Kim, Da Yeon,Jung, Seok Yun,Kim, Yeon Ju,Kang, Songhwa,Park, Ji Hye,Ji, Seung Taek,Jang, Woong Bi,Lamichane, Shreekrishna,Lamichane, Babita Dahal,Chae, Young Chan,Lee, Dongjun,Chung, Joo Seop,Kwon, Sa The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells

Ji, Seung Taek,Kim, Yeon-Ju,Jung, Seok Yun,Kim, Da Yeon,Kang, Songhwa,Park, Ji Hye,Jang, Woong Bi,Ha, Jongseong,Yun, Jisoo,Kwon, Sang-Mo Elsevier 2018 Biochemical and biophysical research communication Vol.499 No.3

<P><B>Abstract</B></P> <P>Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs. We found that short-term priming with OLP attenuated H<SUB>2</SUB>O<SUB>2</SUB>-induced apoptosis by regulating the pro-apoptotic marker Bax and the anti-apoptotic markers Bcl-2 and Mcl-1. Notably, OLP inhibits H<SUB>2</SUB>O<SUB>2</SUB> -induced autophagic cell death by modulating autophagy-related death signals, including mTOR (mammalian target of rapamycin), ULK1 (unc-51 like autophagy activating kinase 1), Beclin-1, AMPK (AMP-activated protein kinase), and LC3 (microtubule-associated protein 1a/1b-light chain 3). Our data suggest that OLP might reduce H<SUB>2</SUB>O<SUB>2</SUB>-induced autophagy and cell apoptosis in MSCs by regulating both the AMPK-ULK axis and the Bcl-2-Mcl-1 axis. Consequently, short-term cell priming with OLP might enhance the therapeutic effect of MSCs against ischemic vascular diseases, which provides an important potential improvement for emerging therapeutic strategies.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Oleuropein (OLP) is a bioactive compound isolated from <I>Olea europaea L.</I> </LI> <LI> Autophagy signals play an important role in cell death decisions and can protect cells by preventing apoptosis. </LI> <LI> Cytoprotective effect exerted by OLP against H<SUB>2</SUB>O<SUB>2</SUB>-induced cell apoptosis and autophagic cell death in hMSCs. </LI> </UL> </P>

Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities

Kim, Yeon-Ju,Ji, Seung Taek,Kim, Da Yeon,Jung, Seok Yun,Kang, Songhwa,Park, Ji Hye,Jang, Woong Bi,Yun, Jisoo,Ha, Jongseong,Lee, Dong Hyung,Kwon, Sang-Mo Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.6

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of $CD34^+$ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against $H_2O_2$-induced oxidative stress via the augmented expression of Bcl-2, a pro-survival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.