• Title/Summary/Keyword: Chemical Reaction Network

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Heme Oxygenase-1 as a Potential Therapeutic Target for Hepatoprotection

  • Farombi, Ebenezer Olatunde;Surh, Young-Joon
    • BMB Reports
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    • v.39 no.5
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    • pp.479-491
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    • 2006
  • Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

Electrochemical Behavior of Well-dispersed Catalysts on Ruthenium Oxide Nanofiber Supports (루테늄 산화물 나노 섬유 지지체에 담지된 고 분산성 촉매의 전기화학적 거동)

  • An, Geon-Hyoung;Ahn, Hyo-Jin
    • Journal of Powder Materials
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    • v.24 no.2
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    • pp.96-101
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    • 2017
  • Well-dispersed platinum catalysts on ruthenium oxide nanofiber supports are fabricated using electrospinning, post-calcination, and reduction methods. To obtain the well-dispersed platinum catalysts, the surface of the nanofiber supports is modified using post-calcination. The structures, morphologies, crystal structures, chemical bonding energies, and electrochemical performance of the catalysts are investigated. The optimized catalysts show well-dispersed platinum nanoparticles (1-2 nm) on the nanofiber supports as well as a uniform network structure. In particular, the well-dispersed platinum catalysts on the ruthenium oxide nanofiber supports display excellent catalytic activity for oxygen reduction reactions with a half-wave potential ($E_{1/2}$) of 0.57 V and outstanding long-term stability after 2000 cycles, resulting in a lower $E_{1/2}$ potential degradation of 19 mV. The enhanced electrochemical performance for oxygen reduction reactions results from the well-dispersed platinum catalysts and unique nanofiber supports.

Synthesis of Novel Network Polyesters Containing Malonate Group in Main Chain and Their Fluorescence Image Patterning via Photodegradation (주사슬에 말로네이트기를 가지는 신규 폴리에스테르의 합성과 광분해 특성을 이용한 형광 이미지 패터닝)

  • Jeong, Seon-Ju;Kwak, Gi-Seop;Jung, In-Tae;Lee, Dong-Ho;Roh, Hyung-Jin;Yoon, Keun-Byoung
    • Polymer(Korea)
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    • v.32 no.1
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    • pp.56-62
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    • 2008
  • Three types of network polyesters have been newly synthesized by a two-step condensation reaction by the various combination of several diols and diacids. When these polymer films were thermally treated at $240^{\circ}C$, they exhibited absorptions in a visible range despite the forbidden transition of carbonyl group. When excited at wavelengths above 330 nm, the polymers showed fluorescences in a wide visible range from blue to near yellow. These fluorescence phenomena are due to the formation of certain conjugated structures by the Knoevenagel type self-condensation under the high-temperature thermal treatment. These polymers showed significant difference in the thermal properties as a function of the degrees of chemical crosslinking. They also underwent photodegradation. Highly resolved, fluorescent image patterns were successfully obtained by the photodegradation of malonate group under a strong UV-light irradiation.

Comprehensive Evaluation System for Post-Metabolic Activity of Potential Thyroid-Disrupting Chemicals

  • Yurim Jang;Ji Hyun Moon;Byung Kwan Jeon;Ho Jin Park;Hong Jin Lee;Do Yup Lee
    • Journal of Microbiology and Biotechnology
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    • v.33 no.10
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    • pp.1351-1360
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    • 2023
  • Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.

Computational Drug Discovery Approach Based on Nuclear Factor-κB Pathway Dynamics

  • Nam, Ky-Youb;Oh, Won-Seok;Kim, Chul;Song, Mi-Young;Joung, Jong-Young;Kim, Sun-Young;Park, Jae-Seong;Gang, Sin-Moon;Cho, Young-Uk;No, Kyoung-Tai
    • Bulletin of the Korean Chemical Society
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    • v.32 no.12
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    • pp.4397-4402
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    • 2011
  • The NF-${\kappa}B$ system of transcription factors plays a crucial role in inflammatory diseases, making it an important drug target. We combined quantitative structure activity relationships for predicting the activity of new compounds and quantitative dynamic models for the NF-${\kappa}B$ network with intracellular concentration models. GFA-MLR QSAR analysis was employed to determine the optimal QSAR equation. To validate the predictability of the $IKK{\beta}$ QSAR model for an external set of inhibitors, a set of ordinary differential equations and mass action kinetics were used for modeling the NF-${\kappa}B$ dynamic system. The reaction parameters were obtained from previously reported research. In the IKKb QSAR model, good cross-validated $q^2$ (0.782) and conventional $r^2$ (0.808) values demonstrated the correlation between the descriptors and each of their activities and reliably predicted the $IKK{\beta}$ activities. Using a developed simulation model of the NF-${\kappa}B$ signaling pathway, we demonstrated differences in $I{\kappa}B$ mRNA expression between normal and different inhibitory states. When the inhibition efficiency increased, inhibitor 1 (PS-1145) led to long-term oscillations. The combined computational modeling and NF-${\kappa}B$ dynamic simulations can be used to understand the inhibition mechanisms and thereby result in the design of mechanism-based inhibitors.

Self-Assembly of Three-Dimensional Copper(II) Macrocyclic Complex with 2,5-Pyridinedicarboxylate Linked by Hydrogen Bond (수소 결합에 의한 삼차원의 Copper(II) 거대고리 착물과 2,5-Pyridinedicarboxylate와의 자기조립)

  • Ki-Young Choi;Haiil Ryu;Yong-Son Kim
    • Journal of the Korean Chemical Society
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    • v.47 no.2
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    • pp.104-108
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    • 2003
  • The reaction of $[Cu(L)]Cl_2{\cdot}H_2O(L=3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0^{1.18},0^{7.12}]docosane)$ with 2,5-pyridinedicarboxylate(pdc) led to the formation of $[Cu(L)(H_2O)](pdc){\cdot}6H_2O(1)$. The structure was characterized by X-ray crystallography and spectroscopic method. The coordination geometry around the copper atom is a distorted square-pyramid with four secondary amines of the macrocycle occupying the basal sites and a water molecule at the axial position. Intermolecular hydrogen bonds in 1 form a three-dimensional molecular network.

Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering

  • Lee, Jin Hyun
    • Biomaterials Research
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    • v.22 no.4
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    • pp.235-248
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    • 2018
  • Background: Injectable hydrogels have been extensively researched for the use as scaffolds or as carriers of therapeutic agents such as drugs, cells, proteins, and bioactive molecules in the treatment of diseases and cancers and the repair and regeneration of tissues. It is because they have the injectability with minimal invasiveness and usability for irregularly shaped sites, in addition to typical advantages of conventional hydrogels such as biocompatibility, permeability to oxygen and nutrient, properties similar to the characteristics of the native extracellular matrix, and porous structure allowing therapeutic agents to be loaded. Main body: In this article, recent studies of injectable hydrogel systems applicable for therapeutic agent delivery, disease/cancer therapy, and tissue engineering have reviewed in terms of the various factors physically and chemically contributing to sol-gel transition via which gels have been formed. The various factors are as follows: several different non-covalent interactions resulting in physical crosslinking (the electrostatic interactions (e.g., the ionic and hydrogen bonds), hydrophobic interactions, ${\pi}$-interactions, and van der Waals forces), in-situ chemical reactions inducing chemical crosslinking (the Diels Alder click reactions, Michael reactions, Schiff base reactions, or enzyme-or photo-mediated reactions), and external stimuli (temperatures, pHs, lights, electric/magnetic fields, ultrasounds, or biomolecular species (e.g., enzyme)). Finally, their applications with accompanying therapeutic agents and notable properties used were reviewed as well. Conclusion: Injectable hydrogels, of which network morphology and properties could be tuned, have shown to control the load and release of therapeutic agents, consequently producing significant therapeutic efficacy. Accordingly, they are believed to be successful and promising biomaterials as scaffolds and carriers of therapeutic agents for disease and cancer therapy and tissue engineering.

The Effects of a Chain Extending Agent and Crosslinking Agent on the Toughness of Castor Oil based Polyurethane-Epoxy IPNs (Castor Oil형 폴리우레탄-에폭시 IPNs에서 사슬연장제와 가교제의 영향에 의한 강인성)

  • Kim, Jong-Seok;Yang, Yeong-Seok
    • Applied Chemistry for Engineering
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    • v.10 no.5
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    • pp.639-643
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    • 1999
  • Interpenetrating polymer networks(IPNs) composed of castor oil(CO) polyurethane(PU) and epoxy resin were prepared by the simultaneous polymerization technique. Two types of PU were prepared using 1,4-butanediol(BD) and BD/trimethylolpropane(TMP) as a chain extending agent and crosslinking agent. The PU/epoxy based on BD as a chain extending agent showed more shift in the damping peak than PU/epoxy based on BD/TMP as the PU content was increased. BDPU/epoxy simultaneous interpenetrating polymer networks(SINs) had a better compatibility than BD/TMP-PU/epoxy SINs. For both systems, it was postulated that unique network formation of PU/epoxy SINs as a chain extending agent and crosslinking agent had occurred to a significant extent of phase mixing. The types of chain extender in the PU were found to be an important factor in determining the phase mixing of the IPNs. When the BD/TMP-PU reaction was faster than epoxy network, the extent of phase mixing was retarded by decreasing entanglement of networks. It was found that both PU/epoxy SINs provided enhanced flexural properties and fracture toughness, fracture surfaces of BDPU/epoxy and BD/TMP-PU/epoxy SINs showed the localized shear deformation and generation of stress whitening associated with the cavitation.

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An Assessment of Air Quality Using Statistical Analysis in Gwangju Area (통계분석을 이용한 광주지역 대기오염도)

  • Seo Gwang Yeob;Paik Ke Jin;Shin Dae Yewn
    • Journal of Environmental Health Sciences
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    • v.30 no.5 s.81
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    • pp.417-426
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    • 2004
  • We investigate changing characteristics and concentration distribution of ambient air quality using data from which obtained local ambient air monitoring network and local meterological measuring sites in Gwangju area from January to December in 2003. Sulfur dioxide ($SO_2$) showed that increase from 8 AM and decrease in 6 PM but, it was not drastically changed concentration. it also 0.010 ppm in 1995 from at this time it's decrease step by step and than some constant in year 2001 to 2003. Nitrogen dioxide ($NO_2$) concentration was showed highest peak in 10 AM and increase again at 6 PM. And also it showed peak concentration (0.026 ppm) in 2001 and decreased from after that times. Ozone was showed peak concentration in 1 PM and Nitrogen dioxide was ditto in 10 AM from this data, we can conclude that this two article ws showed chemical reaction by 3 to 5 hours. There was no case of Ozone alarm in Gwangju area since 1995, but it showed highest ozone concentration (over 0.070 ppm) in May and June of the year and 2 to 4 PM of the day and sometimes it showed increase at the dawn. Ozone product optimum condition was that air temperature is over $25^{\circ}C$, no rain and increase solar radiation (over $20MJ/m^2$) and no wind or below 2.0 m/s wind speed.

Differential Expression of Gene Profiles in MRGX-treated Lung Cancer

  • Kwon, Yong-Kyun;Lee, Seung-Yeul;Kang, Hwan-Soo;Sung, Jung-Suk;Cho, Chong-Kwan;Yoo, Hwa-Seung;Shin, Seungjin;Choi, Jong-Soon;Lee, Yeon-Weol;Jang, Ik-Soon
    • Journal of Pharmacopuncture
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    • v.16 no.3
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    • pp.30-38
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    • 2013
  • Objectives: Modified regular ginseng extract (MRGX) has stronger anti-cancer activity-possessing gensenoside profiles. Methods: To investigate changes in gene expression in the MRGX-treated lung cancer cells (A549), we examined genomic data with cDNA microarray results. After completing the gene-ontology-based analysis, we grouped the genes into up-and down-regulated profiles and into ontology-related regulated genes and proteins through their interaction network. Results: One hundred nine proteins that were up- and down-regulated by MRGX were queried by using IPA. IL8, MMP7 and PLAUR and were found to play a major role in the anti-cancer activity in MRGX-treated lung cancer cells. These results were validated using a Western blot analysis and a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Conclusions: Most MRGX-responsive genes are up-regulated transiently in A549 cells, but down-regulated in a sustained manner in lung cancer cells.