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- 저자 : Kim Jisook (검색결과 117 건)
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Kim, Chun-Hyung,Han, Baek-Soo,Moon, Jisook,Kim, Deog-Joong,Shin, Joon,Rajan, Sreekanth,Nguyen, Quoc Toan,Sohn, Mijin,Kim, Won-Gon,Han, Minjoon,Jeong, Inhye,Kim, Kyoung-Shim,Lee, Eun-Hye,Tu, Yupeng,Naf National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.28
<P><B>Significance</B></P><P>Parkinson’s disease (PD) is the most prevalent movement disorder with no available treatments that can stop or slow down the disease progress. Although the orphan nuclear receptor Nurr1 is a promising target for PD, it is thought to be a ligand-independent transcription factor and, so far, no small molecule has been identified that can bind to its ligand binding domain. Here, we established high throughput cell-based assays and successfully identified three Nurr1 agonists among FDA-approved drugs, all sharing an identical chemical scaffold. Remarkably, these compounds not only directly bind to Nurr1 but also ameliorate behavioral defects in a rodent model of PD. Thus, our study shows that Nurr1 could serve as a valid drug target for neuroprotective therapeutics of PD.</P><P>Parkinson’s disease (PD), primarily caused by selective degeneration of midbrain dopamine (mDA) neurons, is the most prevalent movement disorder, affecting 1–2% of the global population over the age of 65. Currently available pharmacological treatments are largely symptomatic and lose their efficacy over time with accompanying severe side effects such as dyskinesia. Thus, there is an unmet clinical need to develop mechanism-based and/or disease-modifying treatments. Based on the unique dual role of the nuclear orphan receptor Nurr1 for development and maintenance of mDA neurons and their protection from inflammation-induced death, we hypothesize that Nurr1 can be a molecular target for neuroprotective therapeutic development for PD. Here we show successful identification of Nurr1 agonists sharing an identical chemical scaffold, 4-amino-7-chloroquinoline, suggesting a critical structure–activity relationship. In particular, we found that two antimalarial drugs, amodiaquine and chloroquine stimulate the transcriptional function of Nurr1 through physical interaction with its ligand binding domain (LBD). Remarkably, these compounds were able to enhance the contrasting dual functions of Nurr1 by further increasing transcriptional activation of mDA-specific genes and further enhancing transrepression of neurotoxic proinflammatory gene expression in microglia. Importantly, these compounds significantly improved behavioral deficits in 6-hydroxydopamine lesioned rat model of PD without any detectable signs of dyskinesia-like behavior. These findings offer proof of principle that small molecules targeting the Nurr1 LBD can be used as a mechanism-based and neuroprotective strategy for PD.</P>
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Kim Jisook,Bae Inhwan,Song Jiyoung,Kim Younghoon,Ahn Younggil,Park Hyun‐Ju,Kim Ha Hyung,Kim Dae Kyong 대한화학회 2021 Bulletin of the Korean Chemical Society Vol.42 No.6
Apoptosis inhibitor (IAP) proteins are overexpressed in many cancers and implicated in tumor growth, so the development of antagonist that disrupts with the binding of IAP to their partner protein is a promising therapeutic strategy. In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized monovalent analogues based on imidazopyrazinone structure of 9. Optimization of cellular potency led to the identification of 17, which showed increase of submicromolar activity (GI50 = 234 nM) and caspase-3 activation (6.3-fold) in MDA-MB-231 breast cancer cells. These findings clearly show the potential for 17 as a promising monovalent antagonist for the development of an effective anticancer treatment.
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Kim, Han Wool,Lee, Hyun-Seob,Kang, Jun Mo,Bae, Sang-Hun,Kim, Chul,Lee, Sang-Hun,Schwarz, Johannes,Kim, Gi Jin,Kim, Jin-Su,Cha, Dong Hyun,Kim, Joopyung,Chang, Sung Woon,Lee, Tae Hee,Moon, Jisook Cognizant Communication Corp. 2018 CELL TRANSPLANTATION Vol. No.
<P>Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.</P>
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Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report
Kim Sung Eun,Lee Na Yeong,Cho Won Kyoung,Yim Jisook,Lee Jae Wook,Kim Myungshin,Chung Jae Hee,Jung Min Ho,Suh Byung-Kyu,Ahn Moon Bae 대한소아내분비학회 2022 Annals of Pediatirc Endocrinology & Metabolism Vol.27 No.4
Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.
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( Jisook Yoo ),( Jung Min Bae ),( Miri Kim ),( Min-soo Kim ),( Mihn-sook Jue ),( Hyang-joon Park ),( Young Bok Lee ),( Kwang-hyun Choi ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2
Background: The association between autoimmune rheumatic diseases (ARDs) and vasculitis, in view of the autoimmunity, should be elucidated by population based cohort study. Objectives: We aimed to evaluate the incidence of vasculitis in various ARDs patients compared with the general population. Methods: This study was designed as a retrospective, population-based cohort study using data from the National Health Insurance system from Jan 2009 until Dec 2013. The incidence of vasculitis in 7 ARDs groups, including systemic lupus erythematosus (SLE), dermatopolymyositis (DMPM), systemic sclerosis (SSc), Sjogren syndrome (SS), Behcet’s disease (BD), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), were compared to that of healthy group. Results: Total number of ARDs patients were 82,550; SLE (n=11,797), DMPM (n=1,340), SSc (n=1,687), SS (n=7,750), BD (n=12,765), AS (n=20,988), and RA (n=26,223). The incidence of vasculitis in ARDs was significantly higher than that of healthy control (0.52% vs 0.15%, P<0.0001). Generally, small vessel vasculitis had the higher incidence than that of medium/large vessel vasculitis except SSc (1.30% vs. 0.24%) and DMPM (0.52% vs. 0.37%). Conclusion: As the first nationwide population-based cohort study, we demonstrated an association between vasculitis and ARDs with a statistical significance. The increased incidence of vasculitis in ARDs patients supports the epidemiologic and immunologic similarity.
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Evaluation of aqueous polyamines as CO<sub>2</sub> capture solvents
Kim, Junghwan,Lee, Jisook,Lee, Yunje,Kim, Huiyong,Kim, Eunseok,Lee, Kwang Soon Elsevier 2019 ENERGY Vol.187 No.-
<P><B>Abstract</B></P> <P>Aqueous alkanol amines or their blends are used as solvents for acid gas removal in most amine scrubbing processes. In this study, we selected six polyamines with three amine groups that have sufficiently high boiling temperatures and evaluated their potentials as CO<SUB>2</SUB> capture solvents by investigating the CO<SUB>2</SUB> vapor–liquid equilibrium, mass transfer rate, viscosity, and thermal stability. Among the tested polyamines, two were chosen and mixed with 2-(butylamino)ethanol and piperazine (PZ) to compensate for the inferior properties of each polyamine, and their properties were investigated. As a result, aqueous 2,6,10-trimethyl-2,6,10-triazaundecane mixed with a small amount of PZ showed a great potential as a new CO<SUB>2</SUB> capture solvent in that it has a quite high absorption rate and thermal stability and a low reboiler duty.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The potential of aqueous polyamines as CO<SUB>2</SUB> capture solvents was investigated. </LI> <LI> 6 single amines and 3 mixed amines with promoters were evaluated. </LI> <LI> Evaluation was performed from the viewpoints as follows. </LI> <LI> The reboiler duty, absorption rate and thermal stability through lab experiments. </LI> <LI> P6 mixed with PZ was considered a promising candidate for CO<SUB>2</SUB>-absorbing solvent. </LI> </UL> </P>
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Proteomic Analysis of the Aqueous Humor in Age-related Macular Degeneration (AMD) Patients
Kim, Tae Wan,Kang, Jeong Won,Ahn, Jeeyun,Lee, Eun Kyung,Cho, Kyung-Cho,Han, Bit Na Ra,Hong, Nam Young,Park, Jisook,Kim, Kwang Pyo American Chemical Society 2012 Journal of Proteome Research Vol.11 No.8
<P>Age-related macular degeneration (AMD) can lead to irreversible central vision loss in the elderly. Although large number of growth factor pathways, including the vascular endothelial growth factor (VEGF), has been implicated in the pathogenesis of AMD, no study has directly assessed the whole proteomic composition in the aqueous humor (AH) among AMD patients. The AH contains proteins secreted from the anterior segment tissue, and these proteins may play an important role in the pathogenesis of AMD. Thus, comparisons between the AH proteomic profiles of AMD patients and non-AMD controls may lead to the verification of novel pathogenic proteins useful as potential clinical biomarkers. In this study, we used discovery-based proteomics and Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) to analyze AH from AMD patients and AH from controls who underwent cataract surgery. A total of 154 proteins with at least two unique peptides were identified in the AH. Of these 154 proteins identified by discovery-based proteomics, 10 AH proteins were novel identifications. The protein composition in the AH was different between AMD patients and non-AMD controls. Subsequently, a systematic MRM-MS assay was performed in seven highly abundant differentially expressed proteins from these groups. Differential expression of three proteins was observed in the AH of AMD patients compared with that of cataract controls (<I>p</I> < 0.0312). Elucidation of the aqueous proteome will establish a foundation for protein function analysis and identify differentially expressed markers associated with AMD. This study demonstrates that integrated proteomic technologies can yield novel biomarkers to detect exudative AMD.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2012/jprobs.2012.11.issue-8/pr300080s/production/images/medium/pr-2012-00080s_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr300080s'>ACS Electronic Supporting Info</A></P>
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