• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1782-1789
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• 2012

We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(${\gamma}$-glutamic acid) (${\gamma}$-PGA). ${\gamma}$-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated ${\gamma}$-PGA was synthesized by covalent coupling between the carboxyl groups of ${\gamma}$-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded ${\gamma}$-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated ${\gamma}$-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated ${\gamma}$-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked ${\gamma}$-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels in aqueous solution were $136.3{\pm}37.6$ nm and $-32.5{\pm}5.3$ mV, respectively. The loading amount of Dox was approximately 38.7 ${\mu}g$ per mg of ${\gamma}$-PGA nanogel. The Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1-10 mM). Through fluorescence microscopy and FACS, the cellular uptake of ${\gamma}$-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of ${\gamma}$-PGA nanogels. The bio-derived ${\gamma}$-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.

• Journal of Adhesion and Interface
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• v.4 no.1
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• pp.1-8
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• 2003

In this work, the effect of PMR-15 content on the variation of surface free energy of the DGEBA/PMR-15 blend system was investigated in terms of contact angles and mechanical interfacial tests. Based on FT-IR result of the blend system. C=O (1,772, $1,778cm^{-1}$) and C-N ($1,372cm^{-1}$) peaks appeared with imidization of PMR-15 and -OH ($3,500cm^{-1}$) peak showed broadly at 10 phr of PMR-15 by ring-opening of epoxy. Contact angle measurements were performed by using deionized water and diiodomethane as testing liquids. As a result, the surface free energy of the blends gave a maximum value at 10 phr of PMR-15, due to the significant increasing of specific component. The mechanical interfacial properties measured from the critical stress intensity factor ($K_{IC}$) and the critical strain energy release rate ($G_{IC}$) showed a similar behavior with the results of surface energetics. This behavior was probably attributed to The improving of the interfacial adhesion between intermolecules, resulting from increasing the hydrogen bondings of the blends.

• Food Science and Preservation
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• v.18 no.3
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• pp.358-365
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• 2011

The antioxidant and neuronal cell-protective effects of hot water extract from commercial buckwheat tea (CBTE) were evaluated. The 2,2'-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, ferric reducing antioxidant power (FRAP), and malondialdehyde (MDA) inhibitory effect of the CBTE increased in a dose-dependent manner. The Intracellular reactive oxygen species (ROS) accumulation that resulted from hydrogen peroxide ($H_2O_2$) treatment more significantly decreased when CBTE was present in the media than when the PC12 cells were treated only with $H_2O_2$. In the neuronal cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), the aqueous extracts showed a protective effect against $H_2O_2$-induced neurotoxicity, and the lactate dehydrogenase (LDH) release into the medium was also inhibited by CBTE. The total phenolics of CBTE was 9,608.10 mg/100 g, and the major phenolic compounds were rutin (13.42 mg/100 g) and quercitrin (0.90 mg/100 g). These data suggested that CBTE, including the aforementioned phenolics, may be useful in reducing the risk of neurodegenerative disease.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.329-340
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• 2024

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H₂O₂). The results showed that mangiferin attenuated H₂O₂-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H₂O₂-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H₂O₂-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.383-390
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• 2018

Most neurodegenerative diseases are known to be influenced by oxidative stress. We investigated the anti-oxidative activity of the concentrate of fermented wild ginseng root culture (HLJG0701) containing ginsenosides Rg5 and Rk1. HLJG0701 showed effective DPPH and ABTS radical scavenging ability ($IC_{50}$: 16- and 4-fold dilution, respectively) and was inhibited dose-dependently by the $FeSO_4$-induced lipid peroxidation group (8- and 4-fold dilution: 2.3 and 1.5 nM, respectively). In MTT and LDH assays, 8-, 16-, 32- and 64-fold diluted HLJG0701 significantly increased cell viability by 70, 53, 35, and 26%, respectively. LDH released by HLJG0701 was reduced 1.3-fold with 8-fold diluted HLJG0701 compared to the $H_2O_2$-treated control. In addition, the inhibitory effect of HLJG0701 on oxidative stress in PC12 cells was confirmed by DCF-DA analysis (16-, 4-fold diluted HLJG0701: 50 and 68% ROS inhibition, respectively), TBARS (16- and 4-fold diluted HLJG0701: 50.7 and 46.5% inhibition, respectively), GPx (16- and 4-fold diluted HLJG0701: 133.3 and 227.3% release, respectively), and SOD analysis (16- and 4-fold diluted HLJG0701: 118.2 and 218.2% release, respectively). These results suggested that HLJG0701 protects neuronal cells by its anti-oxidative effects and hence can be a potential preventive material against neurodegenerative diseases.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.46-53
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• 1996

Background: Endotoxin or lipopolysaccharide(LPS) can prime phagocytic cells such as polymorphonuclear leukocytes, monocytes or animal peritoneal macrophages to generate increased amounts of secretory products such as oxygen free radicals and tumor necrosis factor, which play an important role in developing adult respiratory distress syndrome in gram negative sepsis. Human alveolar macrophages(HAM) are continuously exposed to various stimuli inhaled into the alveoli, and the response to LPS might be different in HAM. Therefore, we investigated the effect of LPS pre-exposure on HAM adhered to plastic surface and A549 cell(type II human alveolar epithelial cell line) monolayer. Methods: HAM were isolated from bronchoalveolar lavage fluid from normal lung of the patients with localized lung cancer and esophageal cancer. LPS was exposed to HAM for 2hrs before or after adherence to plastic surface of 24-well Linbro plate and A549 cell monolayer. And then HAM was stimulated with PMA(phorbol myristate acetate) or fMLP(N-formyl-methionylleucyl-phenylalanine). The amount of hydrogen peroxide($H_2O_2$) production in the supernatant was measured on the principle of peroxidase-dependent oxidation of phenol red by hydrogen peroxide. Results: LPS pre-exposure could not enhance $H_2O_2$ production in neither HAM adhered to plastic surface nor one to A549 cell monolayer. But LPS even in the absence of PMA or fMLP stimulation directly increased $H_2O_2$ release in HAM if added after the adherence to A549 cell monolayer. Conclusion: Endotoxin does not prime HAM, but may directly activate HAM adhered to alveolar epithelial cells. Further investagation will be necessary.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• Journal of the Society of Disaster Information
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• v.9 no.4
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• pp.449-461
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• 2013

As the hydrofluoric acid leak in Gumi-si, Gyeongsangbuk-do or hydrochloric acid leak in Ulsan, Gyeongsangnam-do demonstrated, chemical related accidents are mostly caused by large amounts of volatile toxic substances leaking due to the damages of storage tank or pipe lines of transporter. Safety assessment is the most important concern because such toxic material accidents cause human and material damages to the environment and atmosphere of the surrounding area. Therefore, in this study, a hydrofluoric acid leaked from a storage tank was selected as the study example to simulate the leaked substance diffusing into the atmosphere and result analysis was performed through the numerical Analysis and diffusion simulation of ALOHA(Areal Location of Hazardous Atmospheres). the results of a qualitative evaluation of HAZOP (Hazard Operability)was looked at to find that the flange leak, operation delay due to leakage of the valve and the hose, and toxic gas leak were danger factors. Possibility of fire from temperature, pressure and corrosion, nitrogen supply overpressure and toxic leak from internal corrosion of tank or pipe joints were also found to be high. ALOHA resulting effects were a little different depending on the input data of Dense Gas Model, however, the wind direction and speed, rather than atmospheric stability, played bigger role. Higher wind speed affected the diffusion of contaminant. In term of the diffusion concentration, both liquid and gas leaks resulted in almost the same $LC_{50}$ and ALOHA AEGL-3(Acute Exposure Guidline Level) values. Each scenarios showed almost identical results in ALOHA model. Therefore, a buffer distance of toxic gas can be determined by comparing the numerical analysis and the diffusion concentration to the IDLH(Immediately Dangerous to Life and Health). Such study will help perform the risk assessment of toxic leak more efficiently and be utilized in establishing community emergency response system properly.

• Nuclear Engineering and Technology
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• v.39 no.5
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• pp.603-616
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• 2007

Roy Huddle, having invented the coated particle in Harwell 1957, stated in the early 1970s that we know now everything about particles and coatings and should be going over to deal with other problems. This was on the occasion of the Dragon fuel performance information meeting London 1973: How wrong a genius be! It took until 1978 that really good particles were made in Germany, then during the Japanese HTTR production in the 1990s and finally the Chinese 2000-2001 campaign for HTR-10. Here, we present a review of history and present status. Today, good fuel is measured by different standards from the seventies: where $9*10^{-4}$ initial free heavy metal fraction was typical for early AVR carbide fuel and $3*10^{-4}$ initial free heavy metal fraction was acceptable for oxide fuel in THTR, we insist on values more than an order of magnitude below this value today. Half a percent of particle failure at the end-of-irradiation, another ancient standard, is not even acceptable today, even for the most severe accidents. While legislation and licensing has not changed, one of the reasons we insist on these improvements is the preference for passive systems rather than active controls of earlier times. After renewed HTGR interest, we are reporting about the start of new or reactivated coated particle work in several parts of the world, considering the aspects of designs/ traditional and new materials, manufacturing technologies/ quality control quality assurance, irradiation and accident performance, modeling and performance predictions, and fuel cycle aspects and spent fuel treatment. In very general terms, the coated particle should be strong, reliable, retentive, and affordable. These properties have to be quantified and will be eventually optimized for a specific application system. Results obtained so far indicate that the same particle can be used for steam cycle applications with $700-750^{\circ}C$ helium coolant gas exit, for gas turbine applications at $850-900^{\circ}C$ and for process heat/hydrogen generation applications with $950^{\circ}C$ outlet temperatures. There is a clear set of standards for modem high quality fuel in terms of low levels of heavy metal contamination, manufacture-induced particle defects during fuel body and fuel element making, irradiation/accident induced particle failures and limits on fission product release from intact particles. While gas-cooled reactor design is still open-ended with blocks for the prismatic and spherical fuel elements for the pebble-bed design, there is near worldwide agreement on high quality fuel: a $500{\mu}m$ diameter $UO_2$ kernel of 10% enrichment is surrounded by a $100{\mu}m$ thick sacrificial buffer layer to be followed by a dense inner pyrocarbon layer, a high quality silicon carbide layer of $35{\mu}m$ thickness and theoretical density and another outer pyrocarbon layer. Good performance has been demonstrated both under operational and under accident conditions, i.e. to 10% FIMA and maximum $1600^{\circ}C$ afterwards. And it is the wide-ranging demonstration experience that makes this particle superior. Recommendations are made for further work: 1. Generation of data for presently manufactured materials, e.g. SiC strength and strength distribution, PyC creep and shrinkage and many more material data sets. 2. Renewed start of irradiation and accident testing of modem coated particle fuel. 3. Analysis of existing and newly created data with a view to demonstrate satisfactory performance at burnups beyond 10% FIMA and complete fission product retention even in accidents that go beyond $1600^{\circ}C$ for a short period of time. This work should proceed at both national and international level.