• Title/Summary/Keyword: Small molecules

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Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders

  • Das, Soumyadip;Ramakrishna, Suresh;Kim, Kye-Seong
    • Molecules and Cells
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    • v.43 no.3
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    • pp.203-214
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    • 2020
  • Post-translational modifications play major roles in the stability, function, and localization of target proteins involved in the nervous system. The ubiquitin-proteasome pathway uses small ubiquitin molecules to degrade neuronal proteins. Deubiquitinating enzymes (DUBs) reverse this degradation and thereby control neuronal cell fate, synaptic plasticity, axonal growth, and proper function of the nervous system. Moreover, mutations or downregulation of certain DUBs have been found in several neurodegenerative diseases, as well as gliomas and neuroblastomas. Based on emerging findings, DUBs represent an important target for therapeutic intervention in various neurological disorders. Here, we summarize advances in our understanding of the roles of DUBs related to neurobiology.

A Study of Mg Capping Inside p-tert-butylcalix[4]arene Adsorbed on a Ge(100) Surface

  • Shin, Minjeong;Lee, Myungjin;Lee, Hangil
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.08a
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    • pp.135-135
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    • 2013
  • The electronic and adsorption structures of Mg and p-tert-butylcalix[4]arene (p-TBCA) adsorbed onto a Ge(100) surface under a variety of sample conditions were characterized using high-resolution photoemission spectroscopy (HRPES) and their corresponding DFT calculation results. Interestingly, after 0.10 ML p-TBCA molecules had been adsorbed onto a Ge(100) surface, subsequent adsorption of a small amount of metallic Mg (~0.10 ML) resulted in the formation of a capped structure inside the pre-adsorbed p-TBCA molecules. The adsorption structures resulting from further deposition of Mg (~0.50 ML) onto the Ge(100) surface were monitored based on the surface charge state and Mg 2s core level spectrum. Work function measurements clearly indicated the electronic structures of the Mg and p-TBCA adsorbed onto the Ge(100) surface. Moreover, we confirmed that three different adsorption structures are experimentally favorable at room temperature through DFT calculation results.

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Reactive Ion Scattering Study of Ice Surfaces. Proton Transfer and H/D Exchange Reactions

  • Mun, Ui-Seong;Kim, Su-Yeon;Gang, Heon
    • Proceedings of the Korean Vacuum Society Conference
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    • 2010.08a
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    • pp.64-64
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    • 2010
  • Ice film surfaces were examined by using the reactive ion scattering (RIS) of low energy (<35 eV) cesium ion beams. Neutral molecules (X) on the surface were detected in the form of cesium-molecule ion clusters (CsX+). Ionic species on the surface were desorbed from the surface via a low energy sputtering (LES) process below the threshold energy of secondary ion emission. The RIS and LES methods allowed us to study the H/D exchange reactions between H2O and D2O molecules on the surface and the associated proton transfer mechanisms. Specifically, H/D exchange kinetics was examined for D2O ice films (~10 BL) covered with a small amount of H2O (<0.5 BL), in the presence or absence of HCl adsorbates which provided excess protons on the surface.

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The Chemistry of Rhodium in Polysulfone: Reactions with Various Small Gas Molecules

  • Il-Wun Shim;Jin-Si Kim;Seok-Jong Oh;Yong-Sik Yang;Hwan-Kyu Suh;Sang-Kyu Lee
    • Bulletin of the Korean Chemical Society
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    • v.15 no.2
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    • pp.126-132
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    • 1994
  • RhCl [P($C_6H_5)_3]_3$ complexes have been incorporated in polysulfone (PS) as a dispersion medium using cosolvent (THF). The interactions between Rh(Ⅰ) complexes and polysulfone polymer molecules are examined by infrared spectroscopy and thermal analysis. The chemical reactivity of Rh in PS films has been investigated by reacting Rh sites with CO, $H_2,\;D_2,\;O_2\;NO,\;C_2H_2\;and\;C_2H_4$ in the temperature range $25-200^{\circ}C$. Various Rh-carbonyl, -hydride and -nitrosyl species formed in PS films are characterized by their infrared spectra. Rh complexes in PS film show interesting catalytic reactivities in the reactions such as hydrogenation of $C_2H_2\;and\;C_2H_4$, oxidation of CO, and reduction of NO by CO or $H_2$ gas under relatively mild conditions.

The Gelation Studies. of N-Methylolated PAAms in Aqueous Media

  • Cheon-Koog Kim;Jeong-In Sohn
    • Bulletin of the Korean Chemical Society
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    • v.14 no.1
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    • pp.34-34
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    • 1993
  • The gelation phenomena of N-methylolated PAAm (M-PAAm) in aqueous media was studied. The critical gelation concentration (CGC) was very close to the calculated $C^*$ of the scaling theory. But the CGC of lower MW M-PAAm deviated from $C^*$ due to contamination of small molecules. We propose that the CGC is the close packing configuration of polymer molecules in solution. The experimental results of the gelation of M-PAAm/PAAm mixture proved that the close packing configuration is essential to make a gel. We calculated the minimum quantity of M-PAAm to make M-PAAm/PAAm mixture a gel by using the close packing configuration. We used a lattice model.

Manufacturing Therapeutic Exosomes: from Bench to Industry

  • Ahn, So-Hee;Ryu, Seung-Wook;Choi, Hojun;You, Sangmin;Park, Jun;Choi, Chulhee
    • Molecules and Cells
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    • v.45 no.5
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    • pp.284-290
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    • 2022
  • Exosome, a type of nanoparticles also known as small extracellular vesicles are gaining attention as novel therapeutics for various diseases because of their ability to deliver genetic or bioactive molecules to recipient cells. Although many pharmaceutical companies are gradually developing exosome therapeutics, numerous hurdles remain regarding manufacture of clinical-grade exosomes for therapeutic use. In this mini-review, we will discuss the manufacturing challenges of therapeutic exosomes, including cell line development, upstream cell culture, and downstream purification process. In addition, developing proper formulations for exosome storage and, establishing good manufacturing practice facility for producing therapeutic exosomes remains as challenges for developing clinical-grade exosomes. However, owing to the lack of consensus regarding the guidelines for manufacturing therapeutic exosomes, close communication between regulators and companies is required for the successful development of exosome therapeutics. This review shares the challenges and perspectives regarding the manufacture and quality control of clinical grade exosomes.

Gelation of silk fibroin solution via β-sheet formation promoted by riboflavin-mediated photo-crosslinking

  • Choi, Jaeho;Ki, Chang Seok
    • International Journal of Industrial Entomology and Biomaterials
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    • v.45 no.1
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    • pp.12-16
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    • 2022
  • Di-tyrosine photo-crosslinking of silk fibroin (SF) is recently highlighted as a biocompatible hydrogel fabrication process, because this method does not need potentially harmful chemical species. However, the resulting crosslinking density is often insufficient to obtain a mechanically stiff hydrogel unless additional oxygen is provided during the reaction. In this study, we proposed a combinational crosslinking method to form an SF hydrogel via the di-tyrosine photo-crosslinking with riboflavin (photoinitiator) and physical interaction of SF chains. In the UV light-irradiated SF solution, small particles formed and these particles promoted β-sheet formation of SF molecules, resulting in quick gelation. The di-tyrosine photo-crosslinking produced nuclei that might trigger regular assembly of SF molecules in high temperature condition. Conclusively, this process would contribute to a development of biocompatible hydrogel fabrication for biomedical uses of SF hydrogels.

Siderophore Biosynthesis and Transport Systems in Model and Pathogenic Fungi

  • Sohyeong Choi;James W. Kronstad;Won Hee Jung
    • Journal of Microbiology and Biotechnology
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    • v.34 no.8
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    • pp.1551-1562
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    • 2024
  • Fungi employ diverse mechanisms for iron uptake to ensure proliferation and survival in iron-limited environments. Siderophores are secondary metabolite small molecules with a high affinity specifically for ferric iron; these molecules play an essential role in iron acquisition in fungi and significantly influence fungal physiology and virulence. Fungal siderophores, which are primarily hydroxamate types, are synthesized via non-ribosomal peptide synthetases (NRPS) or NRPS-independent pathways. Following synthesis, siderophores are excreted, chelate iron, and are transported into the cell by specific cell membrane transporters. In several human pathogenic fungi, siderophores are pivotal for virulence, as inhibition of their synthesis or transport significantly reduces disease in murine models of infection. This review briefly highlights siderophore biosynthesis and transport mechanisms in fungal pathogens as well the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Understanding siderophore biosynthesis and transport in pathogenic fungi provides valuable insights into fungal biology and illuminates potential therapeutic targets for combating fungal infections.

H9 Induces Apoptosis via the Intrinsic Pathway in Non-Small-Cell Lung Cancer A549 Cells

  • Kwon, Sae-Bom;Kim, Min-Je;Sun Young, Ham;Park, Ga Wan;Choi, Kang-Duk;Jung, Seung Hyun;Do-Young, Yoon
    • Journal of Microbiology and Biotechnology
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    • v.25 no.3
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    • pp.343-352
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    • 2015
  • H9 is an ethanol extract prepared from nine traditional/medicinal herbs. This study was focused on the anticancer effect of H9 in non-small-cell lung cancer cells. The effects of H9 on cell viability, apoptosis, mitochondrial membrane potential (MMP; ${\Delta}\psi_{m}$), and apoptosisrelated protein expression were investigated in A549 human lung cancer cells. In this study, H9-induced apoptosis was confirmed by propidium iodide staining, expression levels of mRNA were determined by reverse transcriptase polymerase chain reaction, protein expression levels were checked by western blot analysis, and MMP (${\Delta}\psi_{m}$) was measured by JC-1 staining. Our results indicated that H9 decreased the viability of A549 cells and induced cell morphological changes in a dose-dependent manner. H9 also altered expression levels of molecules involved in the intrinsic signaling pathway. H9 inhibited Bcl-xL expression, whereas Bax expression was enhanced and cytochrome C was released. Furthermore, H9 treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase; the MMP was collapsed by H9. However, the expression levels of extrinsic pathway molecules such as Fas/FasL, TRAIL/TRAIL-R, DR5, and Fas-associated death receptor were downregulated by H9. These results indicated that H9 inhibited proliferation and induced apoptosis by activating intrinsic pathways but not extrinsic pathways in human lung cancer cells. Our results suggest that H9 can be used as an alternative remedy for human non-small-cell lung cancer.

Correlation Between Expression of Cell Adhesion Molecules CD44 v6 and E-cadherin and Lymphatic Metastasis in Non-small Cell Lung Cancer

  • Su, Chong-Yu;Li, Yun-Song;Han, Yi;Zhou, Shi-Jie;Liu, Zhi-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2221-2224
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    • 2014
  • Objective: To explore the relationship between expressions of cell adhesion molecules CD44 v6 and E-cadherin (E-cad) and lymphatic metastasis in non-small cell lung cancer (NSCLC). Materials and Methods: Eightyseven tissue samples obtained from patients with primary NSCLC were collected in our hospital from Dec., 2007 to Dec., 2012, and the expressions of CD44 v6 and E-cad gene proteins in these samples were detected by immunohistochemical method. Results: In the tissue without lymphatic metastasis, the positive expression rate of CD44 v6 was significantly lower, whereas the normal expression rate of E-cad was notably higher than that with lymphatic metastasis (55.6% vs. 78.4%, 47.2% vs. 21.6%), and both differences had statistical significance (P<0.05). Besides, CD44 v6 and E-cad expressions had a significant correlation in the NSCLC tissue with lymphatic metastasis (P<0.05). Conclusions: The positive expression of CD44 v6 and abnormal expression of E-cad may play a very important role in promoting lymphatic metastasis of NSCLC, with synergistic effect. Hence, detection of CD44 v6 and E-cad expressions is conductive to judging the lymphatic metastasis in NSCLC.