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Shim, Man Kyu,Park, Jooho,Yoon, Hong Yeol,Lee, Sangmin,Um, Wooram,Kim, Jong-Ho,Kang, Sun-Woong,Seo, Joung-Wook,Hyun, Soo-Wang,Park, Jae Hyung,Byun, Youngro,Kwon, Ick Chan,Kim, Kwangmeyung Elsevier 2019 Journal of controlled release Vol.294 No.-
<P><B>Abstract</B></P> <P>Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition. The carrier-free nanoparticles of FRRG-DOX induced cytotoxicity against cathepsin B-overexpressed tumor cells whereas the toxicity was minimized in normal cells. In particular, the FRRG-DOX nanoparticles showed the successful tumor-targeting ability and enhanced therapeutic efficiency in human colon adenocarcinoma (HT-29) tumor-bearing mice <I>via</I> enhanced permeation and retention (EPR) effect. Furthermore, FRRG-DOX nanoparticles did not present any severe toxicity, such as non-specific cell death and cardiac toxicity, in normal tissues due to minimal expression of cathepsin B. This carrier-free nanoparticles of FRRG-DOX can solve the unavoidable problems of current nanomedicine, such as lower targeting efficiency, toxicity of nanoparticles themselves, and difficulty in mass production that are fatally caused by natural and synthetic nano-sized carriers.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Kyu-Man Shim(심규만),Eun-Joo Hahn(한은주),Won-Kyung Jeon(전원경),Kee-Yoeup Paek(백기엽) 한국원예학회 2010 원예과학기술지 Vol.28 No.2
노니(Morida citrifolia)의 세포 배양과 2차 대사산물 축적에 적합한 배지 조성을 알기 위해 배지 내 옥신(2,4-D, NAA, IBA: 0, 1.0, 3.0, 5.0, 7.0 and 9.0㎎?L<SUP>-1</SUP>), 싸이토키닌(Kinetin, BA: 0, 0.1, 0.3, 0.5, 0.7, and 0.9㎎?L<SUP>-1</SUP>), 무기물 농도(1/4, 1/2, 1, 3/2, 2MS)를 달리하여 3주간 배양하였다. 세포 생장은 NAA 3.0㎎?L<SUP>-1</SUP>, IBA 5.0 또는 7.0㎎?L<SUP>-1</SUP>에서 양호하였으나 2차대사산물의 축적은 옥신 처리에 의해 억제되었다. 옥신과 싸이토키닌의 혼용 효과를 알기 위해 옥신 실험에서 적합한 배지로 선발된 NAA 3㎎?L<SUP>-1</SUP>을 control 로 하여 kinetin과 BA의 농도를 달리하여 실험한 결과, BA 0.9㎎?L<SUP>-1</SUP>를 혼용하였을 때 2차 대사산물 함량이 증가하였다. 세포 생장과 2차 대사산물 함량에 적합한 MS 배지 내 무기물 농도는 서로 달라 세포 생장은 1MS에서, 2차 대사산물 함량은 2MS에서 가장 높았다. 그러나 2MS 배지의 경우, 세포의 고사율이 1MS에 비해 4배 이상 높아 세포 생장에는 치명적이었다. 이상의 결과로, Morinda citrifolia의 세포 배양의 생산성을 증가시키기 위해서는 세포 증식에 적합한 배지를 조성하여 biomass를 최대한 증가시킨 후 2차 대사산물 축적을 위한 배지로 교환하여 배양하는 2단계 배양(Two-stage culture)이 필요하다는 결론을 얻었다. Morida citrifolia cells were cultured with various medium compositions to determine optimal conditions of auxin, cytokinin and medium salt strength for cell biomass and secondary metabolite accumulation. Cell growth was enhanced by NAA (3.0 ㎎?L<SUP>-1</SUP>) and IBA (5.0 and 7.0 ㎎?L<SUP>-1</SUP>), while the accumulation of secondary metabolites (total anthraquinones, phenolics and flavonoids) was inhibited by auxin. The combination of 3.0 ㎎?L<SUP>-1</SUP> NAA and 0.9 ㎎?L<SUP>-1</SUP> BA accelerated the accumulation of secondary metabolites. The optimal MS medium strength for cell biomass and secondary metabolites differed: Cell growth was maximized at 1 MS, while the secondary metabolite contents reached the highest at 2 MS. The results suggested that a two-stage culture method is required for the cell suspension culture of Morinda citrifolia: Two different culture media should be supplied for the accumulation of cell biomass and secondary metabolites.
Kyu-Man Shim,Hosakatte Niranjana Murthy,So-Young Park,Ibrahim Rusli,Kee-Yoeup Paek 한국원예학회 2015 원예과학기술지 Vol.33 No.2
Eurycoma longifolia is an important rare medicinal plant that contains valuable bioactive compounds. In the present study, cell suspension culture of E. longifolia was established for the production of biomass and phenolic compounds. Various medium parameters, such as concentration of auxin, salt strength of the medium, and sucrose and nitrogen concentrations, were optimized for the production of biomass at the flask-scale level. Full strength Murashige and Skoog (MS) medium supplemented with 3.0 ㎎·L<SUP>-1</SUP> naphthaleneacetic acid (NAA), 3% (w/v) sucrose, 0:60 NH₄⁺:NO₃⁻ was found suitable for biomass accumulation. Based on the optimized flask-scale parameters, cell suspension cultures were established in balloon-type bubble bioreactors, and bioprocess parameters such as inoculum density and aeration rate were optimized. Inoculum density of 50 g·L<SUP>-1</SUP> and increasing aeration rate from 0.05 to 0.3 vvm, with increases every 7 days, were suitable for the accumulation of both biomass and phenolic compounds. With the optimized conditions, 14.70 g·L<SUP>-1</SUP> dry biomass, 10.33 ㎎·g<SUP>-1</SUP> DW of phenolics and 3.89 ㎎·g<SUP>-1</SUP> DW of flavonoids could be achieved. Phenolics isolated from the cell biomass showed optimal free radical scavenging activity.
Shim, Kyu-Man,Murthy, Hosakatte Niranjana,Park, So-Young,Rusli, Ibrahim,Paek, Kee-Yoeup Korean Society of Horticultural Science 2015 원예과학기술지 Vol.33 No.2
Eurycoma longifolia is an important rare medicinal plant that contains valuable bioactive compounds. In the present study, cell suspension culture of E. longifolia was established for the production of biomass and phenolic compounds. Various medium parameters, such as concentration of auxin, salt strength of the medium, and sucrose and nitrogen concentrations, were optimized for the production of biomass at the flask-scale level. Full strength Murashige and Skoog (MS) medium supplemented with $3.0mg{\cdot}L^{-1}$ naphthaleneacetic acid (NAA), 3% (w/v) sucrose, 0:60 $NH{_4}^+:NO{_3}^-$ was found suitable for biomass accumulation. Based on the optimized flask-scale parameters, cell suspension cultures were established in balloon-type bubble bioreactors, and bioprocess parameters such as inoculum density and aeration rate were optimized. Inoculum density of $50g{\cdot}L^{-1}$ and increasing aeration rate from 0.05 to 0.3 vvm, with increases every 7 days, were suitable for the accumulation of both biomass and phenolic compounds. With the optimized conditions, $14.70g{\cdot}L^{-1}$ dry biomass, $10.33mg{\cdot}g^{-1}$ DW of phenolics and $3.89mg{\cdot}g^{-1}$ DW of flavonoids could be achieved. Phenolics isolated from the cell biomass showed optimal free radical scavenging activity.
심상일,김성학,박동빈,신규만 대한신경외과학회 1991 Journal of Korean neurosurgical society Vol.20 No.6
From January 1987 to December 1989, Six patients with lipomyelomeningocele were operated. There were 4 females and 2 males. The chief complaints that caused these patients to seek help were cosmetic effect of the mass on back, urinary incontinence, ankle deformity and weak leg. The postoperative results were as follows : Patient treated before developing neurological deficit remained unchanged neurologically. Patient treated after developing neurological deficit were left with neurological sequelae. lipomyelomeningoceles are serious lesion which recommand early prophylactic surgery.
Shim, Wooyoung,Paik, Man Jeong,Nguyen, Duc-Toan,Lee, Jin-Kyu,Lee, Yuwon,Kim, Jae-Ho,Shin, Eun-Hee,Kang, Jin Seok,Jung, Hak-Sung,Choi, Sangdun,Park, Sungsu,Shim, Jeom Soon,Lee, Gwang American Chemical Society 2012 ACS NANO Vol.6 No.9
<P>Magnetic nanoparticles (MNPs) have proven themselves to be useful in biomedical research; however, previous reports were insufficient to address the potential dangers of nanoparticles. Here, we investigated gene expression and metabolic changes based on the microarray and gas chromatography-mass spectrometry with human embryo kidney 293 cells treated with MNPs@SiO(2)(RITC), a silica-coated MNP containing Rhodamine B isothiocyanate (RITC). In addition, measurement of reactive oxygen species (ROS) and ATP analysis were performed to evaluate the effect of MNPs@SiO(2)(RITC) on mitochondrial function. Compared to the nontreated control, glutamic acid was increased by more than 2.0-fold, and expression of genes related to the glutamic acid metabolic pathway was also disturbed in 1.0 μg/μL of MNPs@SiO(2)(RITC)-treated cells. Furthermore, increases in ROS concentration and mitochondrial damage were observed in this MNPs@SiO(2)(RITC) concentration. The organic acids related to the Krebs cycle were also disturbed, and the capacity of ATP synthesis was decreased in cell treated with an overdose of MNPs@SiO(2)(RITC). Collectively, these results suggest that overdose (1.0 μg/μL) of MNPs caused transcriptomic and metabolic disturbance. In addition, we suggest that a combination of gene expression and metabolic profiles will provide more detailed and sensitive toxicological evaluation for nanoparticles.</P>
실험적 뇌혈관연축에 대한 Nimodipine의 효과 : 전자현미경학적 고찰 Electron Microscopic Studies
심상일,신규만 대한신경외과학회 1990 Journal of Korean neurosurgical society Vol.19 No.8-9
In order to evaluate the effect on nimodipine on the cerebral vasospasm, twelve adult mongrel dogs were stuided in this experiment. This animals were divided into 2 groups ; Intracisternal injection of autogenous blood(Group Ⅰ : no treatment group) and intravenous nimodipine administration after intracisternal injection of autogenous blood(Group Ⅱ : treatment group). Nimodipine was administered 12 hours after intracisternal injection of autogenous blood for 7 days. Dogs were sacrificed at 8th day after intracisternal injection of autogenous blood and the ultrastructual changes were studied. The results were as follows : In Group Ⅰ basilar artery showed endothelial cell swelling with distruption of intercellular junction, subendothelial edema and thickening of the internal elastic lamina with marked edematous change. The pathologic changes of arteries in Group Ⅱ were considered more favorable than that of Group Ⅰ. These results suggest that early intravenous treatment with nimodipine is benifical in the treatment of vasospasm of this models.
하이브리드 전문가시스템 개념에 의한 충주 및 소양강 다목적댐의 연계운영을 위한 사용자중심의 GUI 개발
심순보,김만식,고덕구,--,심규철 한국전문가시스템학회 1995 학술대회 Vol.1 No.1
In order to utilize the limited water resources, it is strongly desired to develop a system for optimal operation of the multipurpose reservoir system easily with visualization of inflow, storage, release, and etc. However, in the water resources management problem, the user of reservoir operation models is often trapped in an ambiguous situation because not only are most reservoir operation models very complex but also building their data is not so easy. However, this difficult problem may be approached using concepts of artificial intelligence. Expert systems, one branch of artificial intelligent programming, is used as an interface between the user and models. This fancy user interface help the user to build the data using the database, run the models, analyze the results and decide on the optimal operation rules for the reservoir operation problem. Moreover, the hybrid expert system, one concept of the expert system, lets us make the user interface easily without changing or converting the algorithmic models into an expert system programming language. Using the above concepts, a user friendly Graphical User Interface (GUI) for the Chungju, Soyang, and joint operation for the both reservoir has been developed. Not only 261 optimal operation rules but also 261 judgmental rules or heuristics for the Chungju reservoir have been collected and developed by the CJDP model. For the verification and validation of the developed GUI, a case study in Chungju Reservoir has been described. In this study, the overall concept and implementation of the hybrid expert system are described.