• BMB Reports
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• v.56 no.4
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• pp.234-239
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• 2023

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H₂O₂-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.446-455
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• 2023

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

• Korean Journal of Mineralogy and Petrology
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• v.36 no.3
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• pp.213-220
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• 2023

In this study, we report the effect of starting materials on the grain size in a multi-component system at high pressure experiments. We used two different starting materials, glass and nano powders, to synthesize bridgmanite in the reduced conditions in the presence of calcium-ferrite-phase MgAl₂O₄ to compared the grain size of synthesized samples. After synthesizing the sample at 40 GPa, 2000 K for 20 hrs, the sample from glass showed the grain size of 50-200 nm whereas the one from nano powders has ~500 nm of grains. This difference may come from 1) the temperature of 2000 K which is low enough for glass starting materials to make more crystal nucleis than to grow crystal size or 2) the possible difference in the redox state of starting materials. It is suggested that the using of nano powders is better to synthesize bigger grains in high pressure experiments with multi-component systems rather than using glass starting materials.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.4
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• pp.73-82
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• 2023

Purpose : Cymbopogon citratus, also known as lemongrass, has widely spread around the world and its essential oil is usually applied in food, perfume, and other industrial purposes. In addition, C. citratus has also been used for the treatment of inflammation, digestive disorders, and diabetes in traditional medicine. In this study, the antioxidative activity of C. citratus ethanol extract (CCEE) was analyzed in RAW 264.7 cells through the induction of one of phase II enzymes, heme oxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor (Nrf)2, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt. Methods : The antioxidative activity of CCEE against oxidative stress and its underlying molecular mechanisms were analyzed by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results : The results exhibited that CCEE potently attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS levels in a dose-dependent manner without any cytotoxicity. CCEE treatment significantly induced the expression of HO-1 which is known for its antioxidative capacity. In addition, CCEE treatment significantly upregulated the expression of Nrf2, a corresponding transcription factor for the regulation of antioxidative enzymes, which was in accordance with the HO-1 overexpression. MAPK and PI3K/Akt were also evaluated for their important roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, the potent HO-1 expression was mediated by not extracellular regulated kinase (ERK), c-Jun NH2 terminal kinase (JNK), p38, but phosphoinositide 3-kinase (PI3K) phosphorylation. To confirm the antioxidative activity of CCEE-induced HO-1 expression, oxidative damage was initiated by t-BHP and attenuated by CCEE treatment, which was identified by HO-1 selective inhibitor and inducer. Conclusion : Consequently, CCEE potently induced the HO-1-mediated antioxidative potential through the modulation of Nrf2 and PI3K/Akt signaling pathways in RAW 264.7 cells. These results suggest that CCEE could be a promising strategy for the mitigation against cellular oxidative damage.

• Economic and Environmental Geology
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• v.56 no.6
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• pp.745-764
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• 2023

In the Republic of Congo, Banded iron formations (BIFs) occur in two areas: the Chaillu Massif and the Ivindo Basement Complex, which are segments of the Archean Congo craton outcropping in the northwestern and southwestern parts of the country. They show interesting potential with significant mineral resources reaching 2 Bt and grades up to 60% Fe. BIFs consist mostly of oxide-rich facies (hematite/magnetite), but carbonate-rich facies are also highlighted. They are found across the country within the similar geological sequences composed of amphibolites, gneisses and greenschists. The Post-Archean Australian Shale (PAAS)-normalized patterns of BIFs show enrichment in elements such as SiO₂, Fe₂O₃, CaO, P₂O₅, Cr, Cu, Zn, Nb, Hf, U and depletion in TiO₂, Al₂O₃, MgO, Na₂O, K₂O, Sc, Th, Ba, Zr, Rb, Ni, V. REE diagrams show slight light REEs (rare earth elements; LREEs) compared to heavy REEs (HREEs), and positive La and Eu anomalies. The lithological associations, as well as the very high (Eu/Eu^*)_SN ratios> 1.8 shown by the BIFs, suggest that they are related to Algoma-type BIFs. The positive correlations between Zr and TiO₂, Al₂O₃, Hf suggest that the contamination comes mainly from felsic rocks, while the absence of correlations between MgO and Cr, Ni argues for negligeable contributions from mafic sources. Pr/Pr^* vs. Ce/Ce^* diagram indicates that the Congolese BIFs were formed in basins with redox heterogeneity, which varies from suboxic to anoxic and from oxic to anoxic conditions. They were formed through hydrothermal vents in the seawater, with relatively low proportions of detrital inputs derived from igneous sources through continental weathering. Some Congolese BIFs show high contents in Cr, Ni and Cu, which suggest that iron (Fe) and silicon (Si) have been leached through hydrothermal processes associated with submarine volcanism. We discussed their tectonic setting and depositional environment and proposed that they were deposited in extensional back-arc basins, which also recorded hydrothermal vent fluids.

• Journal of Life Science
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• v.33 no.10
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• pp.776-782
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• 2023

Silymarin, which is derived from dried Silybum marianum (milk thistle) seeds and fruits, possesses various beneficial properties, such as hepatoprotective, antioxidative, anti-inflammatory, and anticancer activity. This research aimed to explore the antioxidative activity of silymarin against oxidative stress and understand its molecular mechanism in RAW 264.7 cells. The study employed cell viability and reactive oxygen species (ROS) formation assays and western blot analysis. The results demonstrated that silymarin effectively reduced intracellular ROS levels induced by lipopolysaccharide (LPS) in a dose-dependent manner without causing any cytotoxic effects. Moreover, silymarin treatment significantly upregulated the expression of heme oxygenase (HO)-1, a phase II enzyme known for its potent antioxidative activity. Additionally, silymarin treatment significantly induced the expression of nuclear factor-erythroid 2 p45-related factor (Nrf) 2, a transcription factor responsible for regulating antioxidative enzymes, which was consistent with the upregulated HO-1 expression. To investigate the involvement of key signaling pathways in maintaining cellular redox homeostasis against oxidative stress, the phosphorylation status of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) was estimated by western blot analysis. The results showed that silymarin potently induced HO-1 expression, which was mediated by the phosphorylation of p38 MAPK. To further validate the antioxidative potential of silymarin-induced HO-1 expression, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was employed and attenuated by silymarin treatment, as identified by a selective inhibitor for each signaling molecule. In conclusion, silymarin robustly enhanced antioxidative activity by inducing HO-1 via the Nrf2/p38 MAPK signaling pathway in RAW 264.7 cells.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.1
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• Research in Plant Disease
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• v.29 no.4
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• pp.363-376
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• 2023

Alternaria black spots or blights in cruciferous crops have been devastating diseases worldwide and led to economic losses in broccoli, Chinese cabbage, kale, radish, rapeseed, etc. These diseases are caused by different Alternaria spp., including A. brassicae, A. brassicicola and A. raphani transmitted from infected seeds or insect vectors. Efforts to excavate disease resistance traits of cruciferous crops against Alternaria black spots or blights have been demonstrated. Genetic resource of disease resistance was investigated in the wild relatives of cruciferous crops, and different cultivars were screened under different inoculation conditions. Development of the disease-resistant lines against Alternaria black spots or blights was also tried via genetic transformation of the cruciferous crops using diverse plant defence-associated genes. Plant immunity activated by pre-treatment with chemicals, i. e. β-amino-n-butyric acid and melatonin, was suggested for reducing Alternaria black spots or blights in cruciferous crops. The disease resistance traits have also been evaluated in model plant Arabidopsis originating from different habitats. Various plant immunity-related mutants showing different disease responses from wild-type Arabidopsis provided valuable information for managing Alternaria black spots or blights in cruciferous crops. In particular, redox regulation and antioxidant responses altered in the Alternaria-infected mutants were discussed in this review.

• Applied Chemistry for Engineering
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• v.35 no.4
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• pp.296-302
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• 2024

An ionic conjugated polymer-iron (III) chloride composite was prepared via in-situ quaternization polymerization of 2-ethynylpyridine (2EP) using iron (III) chloride. Various instrumental methods revealed that the chemical structure of the resulting conjugated polymer (P2EP)-iron (III) chloride composite has the conjugated backbone system having the designed pyridinium ferric chloride complexes. The polymerization mechanism was assumed to be that the activated triple bond of 2-ethynylpyridinium salt, formed at the first reaction step, is easily susceptible to the step-wise polymerization, followed by the same propagation step that contains the propagating macroanion and monomeric 2-ethynylpyridinium salts. The electro-optical and electrochemical properties of the P2EP-FeCl₃ composite were studied. In the UV-visible spectra of P2EP-FeCl₃ composite, the absorption maximum values were 480 nm and 533 nm, and the PL maximum value was 598 nm. The cyclic voltammograms of the P2EP-FeCl₃ composite exhibited irreversible electrochemical behavior between the oxidation and reduction peaks. The kinetics of the redox process of composites were found to be very close to a diffusion-controlled process from the plot of the oxidation current density versus the scan rate.