Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells

( Seulki Park ),( Kidae Kim ),( Keeok Haam ),( Hyun Seung Ban ),( Jung-ae Kim ),( Byoung Chul Park ),( Sung Goo Park ),( Sunhong Kim ),( Jeong-hoon Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.6

Cereblon (CRBN) is a multi-functional protein that acts as a substrate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells. [BMB Reports 2021; 54(6): 305-310]

PEGylated TRAIL ameliorates experimental inflammatory arthritis by regulation of Th17 cells and regulatory T cells

Park, Jong-Sung,Oh, Yumin,Park, Ogyi,Foss, Catherine A.,Lim, Sung Mook,Jo, Dong-Gyu,Na, Dong Hee,Pomper, Martin G.,Lee, Kang Choon,Lee, Seulki Elsevier 2017 Journal of controlled release Vol.267 No.-

<P><B>Abstract</B></P> <P>TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand that can induce apoptosis in cells expressing its cognate death receptors (DRs). Previously, we demonstrated the therapeutic potential of recombinant human TRAIL in experimental rheumatoid arthritis (RA) models. However, the mechanisms of how DR-mediated apoptosis elicits these actions is not known. Here, we show that systemically administering a potent, long-acting PEGylated TRAIL (TRAIL<SUB>PEG</SUB>) is profoundly anti-rheumatic against two complementary experimental RA mouse models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA), <I>via</I> targeting IL-17 secreting Th17 cells and regulatory T cells (Treg). Systemic administration of TRAIL<SUB>PEG</SUB> after disease onset ameliorated the severity of inflammatory arthritis including arthritis indices, paw thickness, cartilage damage and neutrophil infiltration in both CIA and CAIA models. Additionally, the levels of inflammatory molecules (p-p65, ICAM-1, Cox-2, MMP3, and iNOS), pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-6, IL-17) and accumulation of activated macrophages were significantly reduced after the TRAIL<SUB>PEG</SUB> treatment. Importantly, TRAIL<SUB>PEG</SUB> decreased the number of pro-inflammatory Th17 cells in inflamed arthritic joints through TRAIL-induced apoptosis while increasing anti-inflammatory Treg population <I>in vivo</I>. These results suggest that TRAIL<SUB>PEG</SUB> ameliorates autoimmunity by targeting the Th 17-Tregs axis, making it a promising candidate drug for the treatment of RA.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Efficacy of omalizumab in chronic urticaria refractory to conventional therapy: a Korean real-world experiance

( Seulki Lee ),( Shinyoung Song ),( Seha Park ),( Jeongsoo Kim ),( Heejoo Kim ),( Jinok Baek ),( Hyangjoon Park ),( Jooyoung Roh ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

More than fifty percent of the chronic spontaneous urticaria (CSU) patients are resistant to standard dose of H1-antihistamine treatment. Omalizumab is an anti-IgE antibody that has proved to be effective in treatment of patients with chronic urticaria refractory to antihistamines. We treated the CSU patients with omalizumab who respond to treatment with high dose antihistamnine. Nineteen patients (male : female=11 : 8 ; mean age,52.4 years) were treated with 150mg or 300mg omalizumab every 4 weeks more than 12 weeks. The duration of CSU before starting omalizumab ranged between 3 months and 12 years (mean, 4.1 years). Mean serum IgE level was 123.3 IU/ml (range 2-278). Treatment efficacy were assessed primarily based on changes from baseline to week 12 in weekly urticaria activity scores (UAS7) and investigator’s global assessment (IGA). After 12 weeks of therapy, the response was evaluated as follows. Mean UAS7 score decreased from 25.8 at baseline to 3.8 after the 12 weeks and mean IGA score decreased from 3.3 to 0.8 after the 12 weeks. Complete remission (UAS7 =0) was seen in 38% of patients who started with 300mg and in 27% of those who started with 150mg. Partial response (UAS7≤6) was observed in 50% of patients. One patient (5%) had no response to omalizumab treatment. This real world experience demonstrated that omalizumab is a well-tolerated, beneficial option for the treatment of CSU patients refractory to antihistamine.

A case of malignant fibrous histiocytoma on the upper arm

( Seulki Lee ),( Shinyoung Song ),( Seha Park ),( Jeongsoo Kim ),( Heejoo Kim ),( Jinok Baek ),( Jooyoung Roh ),( Hyangjoon Park ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

Malignant fibrous histiocytoma (MFH) is a soft tissue sarcoma that most commonly occurs on the extremities in middle and late adulthood. It has recently been classified as undifferentiated pleomorphic sarcoma (UPS). It has often been confused with other sarcomas because of the highly variable morphologic pattern. Also this tumor has an aggressive biological behavior and a poor prognosis. A 78-year old female presents with 2.0 X 1.0 cm sized tendor, firm, erythematous nodule on left upper arm. That nodule was excised by a primary care dermatologist. Initial pathologic diagnosis was atypical fibroxanthoma. But the tumor recurred locally and grew rapidly (7.0 X 5.0 cm sized) in three months. MFH was suspected and wide excision was performed with negative resection margins. Histopathologic features included pleomorphic cellular morphologies and frequent mitotic figures consistent with MFH. In immunohistochemical staining, the tumor cells were positive with vimentin, CD68 and CD10. It was negative with CD99, S-100 and desmin. The tumor was diagnosed as MFH and there has been no evidence of local recurrence for 6 months. Although the prognosis of recurred MFH is known to be poor, a clear resection could provide better control of the tumor with a lower recurrence risk. Therefore, we suggest a complete wide excision with negative margin is essential for an effective management of MFH.

A novel quasi-solid state dye-sensitized solar cell fabricated using a multifunctional network polymer membrane electrolyte

Park, Sung-Hae,Song, In Young,Lim, Jongchul,Kwon, Young Soo,Choi, Jongmin,Song, Seulki,Lee, Jae-Ryung,Park, Taiho The Royal Society of Chemistry 2013 Energy & environmental science Vol.6 No.5

<P>A series of liquid junction dye-sensitized solar cells (DSCs) was fabricated based on polymer membrane-encapsulated dye-sensitized TiO<SUB>2</SUB> nanoparticles, prepared using a surface-induced cross-linking polymerization reaction, to investigate the dependence of the solar cell performance on the encapsulating membrane layer thickness. The ion conductivity decreased as the membrane thickness increased; however, the long term-stability of the devices improved with increasing membrane thickness. Nanoparticles encapsulated in a thick membrane (<I>ca.</I> 37 nm), obtained using a 90 min polymerization time, exhibited excellent pore filling among TiO<SUB>2</SUB> particles. This nanoparticle layer was used to fabricate a thin-layered, quasi-solid state DSC. The thick membrane prevented short-circuit paths from forming between the counter and the TiO<SUB>2</SUB> electrode, thereby reducing the minimum necessary electrode separation distance. The quasi-solid state DSC yielded a high power conversion efficiency (7.6 → 8.1%) and excellent stability during heating at 65 °C over 30 days. These performance characteristics were superior to those obtained from a conventional DSC (7.5 → 3.5%) prepared using a TiO<SUB>2</SUB> active layer with the same thickness. The reduced electrode separation distance shortened the charge transport pathways, which compensated for the reduced ion conductivity in the polymer gel electrolyte. Excellent pore filling on the TiO<SUB>2</SUB> particles minimized the exposure of the dye to the liquid and reduced dye detachment.</P> <P>Graphic Abstract</P><P>The multifuntional network polymer membrane electrolyte for a thin layered device provides short charge transport pathways, better performances, and excellent long-term stability. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3ee24496b'> </P>

Whole genome sequence of lactic acid bacterium <i>Pediococcus acidilactici</i> strain S1

Park, Gun-Seok,Hong, Sung-Jun,Jung, Byung Kwon,Park, Seulki,Jin, Hyewon,Lee, Sang-Jae,Shin, Jae-Ho,Lee, Han-Seung Elsevier 2017 Brazilian journal of microbiology Vol.48 No.3

<P><I>Pediococcus acidilactici</I> strain S1, a lactic acid-fermenting bacterium, was isolated from makgeolli—a Korean traditional fermented alcoholic beverage. Here we report the 1,980,172 bp (G + C content, 42%) genome sequence of <I>Pediococcus acidilactici</I> strain S1 with 1,525 protein-coding sequences (CDS), of which 47% could be assigned to recognized functional genes. The genome sequence of the strain S1 might provide insights into the genetic basis of the lactic acid bacterium with alcohol-tolerant.</P>

Tunable Nanoporous Network Polymer Nanocomposites having Size-Selective Ion Transfer for Dye-Sensitized Solar Cells (Adv. Energy Mater. 2/2013)

Park, Sung-Hae,Lim, Jongchul,Kwon, Young Soo,Song, In Young,Choi, Jong Min,Song, Seulki,Park, Taiho Wiley (John WileySons) 2013 ADVANCED ENERGY MATERIALS Vol.3 No.2

Stable Dye-Sensitized Solar Cells by Encapsulation of N719-Sensitized TiO2 Electrodes Using Surface-Induced Cross-Linking Polymerization

Park, Sung-Hae,Lim, Jongchul,Song, In Young,Atmakuri, Narender,Song, Seulki,Kwon, Young Soo,Choi, Jong Min,Park, Taiho Wiley (John WileySons) 2012 ADVANCED ENERGY MATERIALS Vol.2 No.2

Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles

Park, Kyeongsoon,Kim, Jong-Ho,Nam, Yun Sik,Lee, Seulki,Nam, Hae Yun,Kim, Kwangmeyung,Park, Jae Hyung,Kim, In-San,Choi, Kuiwon,Kim, Sang Yoon,Kwon, Ick Chan Elsevier 2007 Journal of controlled release Vol.122 No.3

<P><B>Abstract</B></P><P>To improve the <I>in vivo</I> tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20?kDa, GC-100?kDa, and GC-250?kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio. The resulting amphiphilic glycol chitosan–cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20?kDa-NP, GC-100?kDa-NP, and GC-250?kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and <I>in vitro</I> stability, were similar regardless of molecular weight. <I>In vivo</I> tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better <I>in vivo</I> stability, based on a pharmacokinetic improvement in blood circulation time.</P>

이광수의 개조론과 기독교 윤리

박슬기(Park Seulki) 한국현대문학회 2011 한국현대문학연구 Vol.0 No.35

이 논문은 이광수의 「민족개조론」의 핵심 사상인 '민족 개조'의 내적 기원을 탐구하고자 한다. 그간 민족 개조의 사상은 「민족개조론」을 둘러싼 정치/사회적인 맥락에서 논의되어 왔다. 그러나 이광수가 '개조'에 부여한 독특한 의미는 그가 당시에 발표했던 기독교론과 문학론과의 관계 속에서 논의해야만 제대로 구명될 수 있다. 이광수의 문학론은 예술의 미를 포기하고 공리주의로 나아간 것이 아니라, 미를 선과 연결시키는 지점을 통해서 진의 차원으로 고양시키고자 하는데 그 핵심이 있었다. 달리 말해, 이광수의 문학론은 예술=인생=도덕이라는 독특한 삼위일체를 성취하려고 하는 것이다. 문학론이 미를 중심으로 선을 통합시켜 진의 차원으로 고양시키고자 하는데 비해, 그의 정치적 비전은 도덕을 중심으로, 이 윤리적 규범을 보편적 선의 차원으로 확대함으로써 진의 차원으로 고양시키고자 한다. 이 확대의 과정에 작동하고 있는 원동력은 그의 기독교론에서 찾을 수 있다. 기독교 윤리는 개인의 행위나 인격에서 비롯되는 것이 아니라, 믿는다는 차원에서 , 즉 믿는 자만이 의로움을 얻을 것이라는 윤리적 형식을 취하고 있기 때문이다. 이광수는 이 형식을 빌어, 도덕을 보편적인 선으로 확정하고, 민족과 국가의 경계를 넘어서는 초월적 자리에 이를 위치시킨다. 이광수는 「민족개조론」 을 어떤 확신에 입각하여 도출했다. 개조의 구체적인 방법, 소요되는 시일, 앞으로의 전망을 논의하는 이 논설을 관통하고 있는 것은 개조는 도덕적이어야 한다는 것이다. 이 논문은 '민족 개조'와 '도덕'의 관계에 대해, 그가 발표한 문학론과 기독교론을 중심으로 구명하고자 한다. The primary purpose of this paper is to search which Kwangsu Lee's political ideas in MinjokGaejoron is originated in. This political article is related to other literary articles published at same time, so his political ideas are probably associated to view on literature. In Lee's writings on the idea of literature, the arts are designated as representative of the beauty and the virtue. The beauty in a work of arts is able to show its total value only if exalted to the state of the truth through standing the verification process of the moral. In other words, Lee's articles on literatureare purposing to form the unique trinity, art and life and morality. In MinjokGaejoron, Lee asserts that the major problem in Choson is severe immorality of individuals, for improving his community-Choson, it is necessary that each individual has to cultivate one's mind. That is, He expands the moral accomplishment of individuals to rule of social community, furthermore, make the rule a universal and regulative doctrine, the Virtue. There is a leaping between moral act of individuals and morality as universal principle. Christian Ethics is in on the leaping point. On Christian Ethics relied on a Biblical quotation, especially in Romans 1:17, the Justice is based on the Faith for God and the Christ, neither ethical acts nor good works. Lee puts a morality of individuals on position of the Faith, and the Virtue on the Justice. In other words, as Christian Justice is on the Faith, the Virtue of Choson is on moral individual. Based on the form of Christian Ethics, Lee organized his political ideas.