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      • Zoogloea ramigera 115의 응집특성과 그것의 생물고분자를 이용한 중금속 제거

        김재하,현근탁,고영환 제주대학교 1994 논문집 Vol.39 No.-

        폐수처리장의 활성오니로 부터 분리된 Zoogloea ramigera 115 균주의 생육적정 pH와 vitamin 생육인자를 규명하고, C/N 조성비에 따른 균체응집특성에 대해서 조사하였다. 그로부터 균체응집과 직접적으로 관련된 생물고분자를 생산 분리하여 중금속 양이온 흡착능과 제거효율을 측정하였다. Z. ramigera 115의 최적 생육 pH 범위는 6.25에서 7.00이었고, 생육촉진인자로 vit. B? 또는 biotin을 요구하였다. C/N 조성비가 클수록 균체응집능이 개선되는 경향이었으며, C/N 조성비 27이상에서는 응집능이 비교적 안정되었다. C/N 조성비 90에서의 생물고분자 생산량은 34.43g/ℓ였으며, 이는 개선될 여지가 있다고 생각된다. Z. ramigera 115의 배양액으로부터 분리된 고분자물질의 단위량당 중금속 양이온 흡착능은 Cu?와 Cd?에 대해서 각각1.3350 ?mol/mg과 0.3120 ?mol/mg이었다. 개개의 중금속 양이온 농도가 약 5mg/ℓ인 용액을 연속식 반응조로 처리한 결과, Z. ramigera 115의 생물고분자에 의해서, Cu?, Mn?, Cd?, Cr?순으로 각각 77, 75, 43, 20%의 제거효율을 보였다. 회분식 반응조를 사용했을 때도, 이와 거의 유사한 제거효율을 얻었다. Z. ramigera 115가 생산하는 고분자의 중금속 이온 흡착능과 응집능을 폐수처리나 중금속 이온의 회수에 이용할 수 있는 실질적인 방법이 모색될 수 있을 것이다. Optimum pH and vitamin requirement for the growth of Zoogloea ramigera 115 which was originally isolated from an active sludge in wastewater treatment plant were determined. Effect of C/N ratio on floc formation by the strain 115 was also investigated. Biopolymer known to be directly involved in flocculation was isolated and tested for its sorption capacity of metal cations. The optimum pH for cell growth was between 6.25 and 7.00, and a biotin or a vit. B.? was required as a growth factor. Although the increase in C/N ratio stimulated floc formation, C/N ratios over 27 showed similar degrees of flocculation. The concentration of biopolymer produced by Z ramigera 115 at C/N ratio 90 was 34.43 g/ℓ, which could be improved. The sorption capacity of the biopolymer was 1.3350 ?mol/mg for Cu? and 0.3120 ?mol/mg for Cd?, respectively. When a solution containing about 5 mg/ℓ of each metal cation was treated with the biopolymer in a continuous type reactor, the cations were removed in the order of Cu?>Mn?>Cd?>Cr? with an individual efficiency of 77, 75, 43, and 20%. The batch type reactor also showed similar removal efficiency. The practical approach for the use of biopolymer produced by Z. ramigera 115 needs to be tried in the field of waste-water treatment and heavy metal cation recovery.

      • SCISCIESCOPUS

        Nanoparticle-mediated delivery of oligonucleotides to the blood-brain barrier: <i>in vitro</i> and <i>in situ</i> brain perfusion studies on the uptake mechanisms

        Informa UK Ltd. 2013 JOURNAL OF DRUG TARGETING Vol.21 No.9

        <P>Except for the few exceptions where topical administration is feasible, progress towards broad clinical application of nucleic acid therapeutics requires development of effective systemic delivery strategies. The central nervous system represents a particularly difficult organ for systemic delivery due to the blood-brain barrier. We previously reported a nanoparticulate delivery system for targeted brain delivery of oligonucleotides upon systemic administration, i.e. liposome-encapsulated polyethylenimine/oligonucleotides polyplexes. In this study, cellular uptake and intracellular trafficking of the nanoparticles were further investigated using <I>in situ</I> brain perfusion technique followed by colocalization and fluorescence resonance energy transfer techniques. The brain endothelial uptake and possibly parenchymal accumulation were readily visualized upon administration via internal carotid artery perfusion. The nanoparticles were colocalized with early-endosome antigen, which confirms the brain endothelial uptake through transferrin receptor-mediated endocytosis. Fluorescence resonance energy transfer analysis also suggested the nanoparticles entered the brain endothelial cells while maintaining their integrity. Together, the enhanced brain uptake, as claimed previously, of the antibody-targeted nanoparticles was clearly confirmed with more convincing evidences. In addition, the experimental techniques described here should be applicable to the studies involving nanoparticle-mediated brain delivery of nucleic acid therapeutics.</P>

      • KCI등재
      • KCI등재

        Small molecule tyrosine kinase inhibitors in glioblastoma

        Gayoung Kim,Young Tag Ko 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.4

        Glioblastoma (GBM) is the most commonmalignant primary brain tumor, with poor survival despitetreatment with surgery, radiotherapy, and chemotherapywith temozolomide. Little progress has been made over thelast two decades, and there remain unmet medical needs. Approximately 45% of patients with GBM carry EGFRmutations, and 13% of them possess altered PDGFR genes. Moreover, VEGF/VEGFR mutations are also observed inthe patient population. Tyrosine kinase inhibitors (TKIs)are emerging cancer therapy drugs that inhibit signal transductioncascades affecting cell proliferation, migration, andangiogenesis. Indications for small molecule TKIs havebeen successfully expanded to multiple types of cancer;however, none of the TKIs have been approved for patientswith GBM. In this review, we summarize clinical trials ofsmall molecule TKIs in patients with GBM and plausiblehypotheses for negative clinical study results. We also discussthe potential TKI candidates that presented significantpreclinical outcomes in patients with GBM.

      • Active-targeted pH-responsive albumin-photosensitizer conjugate nanoparticles as theranostic agents

        Battogtokh, Gantumur,Ko, Young Tag The Royal Society of Chemistry 2015 Journal of Materials Chemistry B Vol.3 No.48

        <P>The objective of this study was to develop an active-targeted, pH-responsive albumin-photosensitizer conjugate as a theranostic agent. Herein, a porphyrin derivative photosensitizer, pheophorbide-a (PheoA), was conjugated to bovine serum albumin (BSA) <I>via</I> a <I>cis</I>-aconityl linkage, and the conjugate was then linked with polyethylene glycosylated folate to improve targeting ability. Further, BSA-<I>c</I>-PheoA and folate (FA)-BSA-<I>c</I>-PheoA at a ratio of 2 : 1 were self-assembled to form nanoparticles with a mean hydrodynamic diameter of 121.47 ± 11.60 nm. The release study exhibited that the photosensitizer was released 4.5-fold faster at pH 5.0 than at pH 7.4 when incubated for 24 h. Cellular uptake results showed that the FA-BSA-<I>c</I>-PheoA nanoparticles were readily taken up by B16F10 and MCF7 cancer cells. <I>In vitro</I> phototoxicity results showed that FA-BSA-<I>c</I>-PheoA NPs have higher efficacy on cancer cells compared to simple BSA-<I>c</I>-PheoA NPs. <I>In vivo</I> bioimaging results exhibited that FA-BSA-<I>c</I>-PheoA NPs greatly accumulated into the tumor area as compared to free PheoA. These results show that our prepared FA-BSA-<I>c</I>-PheoA NPs have the potential to be applied as theranostic agents in photodynamic therapy and photodiagnosis of cancer.</P>

      • KCI등재
      • Self-Assembling Micelle-like Nanoparticles with Detachable Envelopes for Enhanced Delivery of Nucleic Acid Therapeutics

        Battogtokh, Gantumur,Ko, Young Tag American Chemical Society 2014 Molecular pharmaceutics Vol.11 No.3

        <P>In spite of the great potential of nucleic acids as therapeutic agents, the clinical application of nucleic acid therapeutics requires the development of effective systemic delivery strategies. In an effort to develop effective nucleic acid delivery systems suitable for clinical application, we previously reported a self-assembling micelle-like nanoparticle that was based on phospholipid–polyethylenimine conjugates, i.e., “micelle-like nanoparticles” (MNPs). In this study, we aimed to improve the system by enhancing the efficiency of intracellular delivery of the payload via pH-responsive detachment of the monolayer envelope and release of the nucleic acid therapeutics upon reaching the target tissues with an acidic pH, e.g., tumors. The acid-cleavable phospholipid–polyethylenimine conjugate was synthesized via hydrazone bond, and acid-cleavable MNPs were then prepared and characterized as before. We evaluated the acid-cleavable MNP construct for <I>in vitro</I> and <I>in vivo</I> nucleic acid delivery efficiency using cultured tumor cells and tumor-bearing mice. The acid-cleavable nanocarrier showed an enhanced cellular delivery at pH 6.5 as compared to pH 7.4, whereas the noncleavable nanocarrier did not show any differences. Tail vein injections also led to enhanced intracellular uptake of the acid-cleavable nanocarrier compared to the noncleavable nanocarrier into tumor cells of tumor-bearing mice although no significant difference was observed in total tumor accumulation.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2014/mpohbp.2014.11.issue-3/mp400579h/production/images/medium/mp-2013-00579h_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/mp400579h'>ACS Electronic Supporting Info</A></P>

      • SCIE

        Mitochondrial-targeted photosensitizer-loaded folate-albumin nanoparticle for photodynamic therapy of cancer

        Battogtokh, Gantumur,Ko, Young Tag Elsevier 2017 NANOMEDICINE Vol.13 No.2

        <P><B>Abstract</B></P> <P>The objective of this study was to develop a mitochondria-targeted photosensitizer (PS) for photodynamic therapy (PDT). Herein, a porphyrin-derivative photosensitizer, pheophorbide-a (PheoA), was conjugated to carboxybutyltriphenylphosphonium (TPP) <I>via</I> a carbodiimide linkage to enhance mitochondrial targeting and TPP-PheoA conjugate was further loaded into folate-cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its biocompatibility. Cellular uptake results showed that TPP-PheoA and TPP-PheoA@FA-chol-BSA NPs were readily taken up by B16F10 and HeLa cells. Further <I>in vitro</I> studies exhibited that TPP-PheoA and its nanoparticle primarily accumulate in the mitochondria, greatly generate ROS, lead mitochondrial disruption and cell apoptosis, and have higher phototoxicity against cancer cells. <I>In vivo</I> bioimaging and the <I>in vivo</I> antitumor studies indicated that TPP-PheoA@FA-chol-BSA NP greatly accumulated in the tumor area and significantly suppress the tumor growth as compared to PheoA@FA-chol-BSA NP in tumor-bearing mice. Taken together, TPP-PheoA@FA-chol-BSA NP could be a promising mitochondria-targeted PS for image-guided PDT.</P> <P><B>Graphical Abstract</B></P> <P>This study demonstrated that TPP-PheoA@FA-chol-BSA NP was internalized upon cells by endocytosis mechanism due to its active targeting ligand and further reached to mitochondria owing to TPP moiety in TPP-PheoA conjugate. Overall, the antitumor PDT efficacy of TPP-PheoA significantly increased.</P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        Effects of Emergency Care-related Health Policies during the COVID-19 Pandemic in Korea: a Quasi-Experimental Study

        Pak Yun-Suk,Ro Young Sun,Kim Se-Hyung,Han So-Hyun,Ko Sung-keun,Kim Taehui,Kwak Young Ho,Heo Tag,Moon Sungwoo 대한의학회 2021 Journal of Korean medical science Vol.36 No.16

        Background: The purpose of this study was to review the nationwide emergency care-related health policies during the coronavirus disease 2019 (COVID-19) pandemic disaster in Korea and to analyze the effects of the policies on the safety of patients who visit emergency departments (EDs) during this period. Methods: This study is a quasi-experiment study. The study population was patients who visited all 402 EDs in Korea between December 31, 2019 and May 13, 2020, using the National Emergency Department Information System (NEDIS) database. The study period was classified into 5 phases according to the level of national crisis warning of infectious disease and the implementation of emergency care-related health policies, and all study phases were 27 days. The primary outcome was in-hospital mortality, and the secondary outcome was length of stay (LOS) in the ED during the COVID-19 outbreak. Results: The number of ED visits during the study period was 2,636,341, and the in-hospital mortality rate was 1.4%. The number of ED visits decreased from 803,160 in phase 1 to 496,619 in phase 5 during the study period. For in-hospital mortality, the adjusted odds ratio (OR) (95% confidence interval) was 0.77 (0.74–0.79) in phase 5 compared to phase 3. Additionally, by subgroup, the ORs were 0.69 (0.57–0.83) for the patients with acute myocardial infarction and 0.76 (0.67–0.87) for severe trauma in phase 5 compared to phase 3. The ED LOS increased while the number of ED visits decreased as the COVID-19 pandemic progressed, and the ED LOS declined after policy implementation (beta coefficient: −5.3 [−6.5 to −4.2] minutes in phase 5 compared to phase 3). Conclusion: Implementing appropriate emergency care policies in the COVID-19 pandemic would have contributed to improving the safety of all emergency patients and reducing in-hospital mortality by preventing excessive deaths.

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