• Journal of the Computational Structural Engineering Institute of Korea
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• v.35 no.4
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• pp.243-248
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• 2022

Weight optimization was performed for a rotorcraft shaft system using one-dimensional Euler-Bernoulli beam elements. Torsion, shaft support stiffness such as bearings, flange mass are all considered. To guarantee structural dynamic stability, eigenvalue analysis was performed to avoid critical speed and tooth mesh excitation form the gearbox. The weight optimization was performed by adjusting the thickness and radius while the length of the shaft was fixed, and the optimization process was divided into two stages. In the first, the weight is optimized with the torsional strength constraint. In the second, the difference between the primary mode of shaft and the critical speed is maximized so that the primary mode of the shaft can avoid the critical speed while the constraint on the torsional strength of the shaft is satisfied according to the standard for shaft system stability (AMC P 706-201, 1974). The proposed method was verified by comparing the results of the optimal design using the given one-dimensional beam elements with the stress results of the 3D finite element and the actual manufactured shaft.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Journal of Veterinary Science
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• v.24 no.2
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• pp.24.1-24.13
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• 2023

Background: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. Objectives: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). Methods: Each EGT concentration (0, 10, 50, and 100 μM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. Results: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 μM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 μM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 μM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. Conclusions: Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Journal of agriculture & life science
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• v.50 no.3
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• pp.129-139
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• 2016

Curcumin plays a protective role in brain injury through its anti-oxidant and anti-inflammatory activities. Moreover, peroxiredoxin-5 exerts a protective effect against oxidative stress. The aim of this study was to investigate whether curcumin modulated the peroxiredoxin-5 expression in focal cerebral ischemic animal model. Middle cerebral artery occlusion(MCAO) was performed to induce cerebral ischemic injury in rats. Adult male rats were injected intraperitoneally with vehicle or curcumin(50mg/kg B.W.) 1 h after MCAO and cerebral cortex tissues were collected 24 h after MCAO. Photographs of hematoxylin and eosin staining showed that MCAO induced necrotic changes with scalloped shrunken form and apoptotic changes with nuclear chromatin condensations. However, curcumin treatment attenuated MCAO-induced histopathological changes. Moreover, this study clearly showed that peroxiredoxin-5 expression was decreased in MCAO operated animal with vehicle using a proteomics approach. However, this decrease in peroxiredoxin-5 expression was attenuated by curcumin treatment. Reverse-transcription PCR and Western blot analyses confirmed that curcumin treatment alleviated the MCAO injury-induced decrease in peroxiredoxin-5 expression(p<0.05). These results demonstrated that curcumin regulates peroxiredoxin-5 expression in MCAO animal model. In conclusion, our findings suggest that curcumin exerts a neuroprotective effect in cerebral ischemia by attenuating the MCAO-induced decrease in peroxiredoxin-5 expression.

• Journal of the Korean Institute of Gas
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• v.27 no.2
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• pp.39-48
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• 2023

This study presents the experimental results to measure the adsorption amount of methane gas by coal according to the conditions of a coalbed methane (CBM) reservoir. Adsorbed gas to coal seam particles was measured under reservoir conditions (normal pressure ~ 1,200 psi pressure range, temperature range15 ~ 45℃) using coal samples obtained from random mines in Kalimantan Island, North Indonesia. The obtained amount of absolute adsorbed gas was applied to triangular with linear interpolation to calculate the maximum amount of adsorbed gas according to temperature and pressure change, at which no experiment was performed. As a result, it was revealed that the amount of adsorbed gas to coal particles increased as the pressure increased and temperature decreased, but the increase of the amount of adsorbed gas decreased at more than an appropriate depth(1,000 ft). In the cleat permeability and cleat porosity for each depth of the coal bed considering the effective stress, the cleat permeability was 28.86 ~ 46.81 md, and the cleat porosity was 0.83 ~ 0.98%. This means that the gas productivity varies significantly with the depth because the reduction of the permeability according to the depth in the coal seam is significant. Therefore, a coalbed depth should be considered essential when designing the spacing of production wells in a coalbed methane reservoir in further study.

• 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.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.682-697
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• 2023

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

• Korean Journal of Agricultural Science
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• v.49 no.2
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• pp.175-184
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• 2022

The present study investigated the neuroprotective effects of Coreopsis lanceolate extract against hydrogen-peroxide (H₂O₂)-induced oxidative damage and cell death in pheochromocytoma 12 (PC12) cells. Reactive oxygen species (ROS), 2,2'-azinobis (3-ethylbebzothiazoloine-6-sulfonic acid) diammonium salt, and 1,1-diphenyl-2-picrrylhydrazyl radical scavenging activities, as well as the expression levels of proteins associated with oxidative damage and cell death were investigated. According to the results, C. lanceolate extract exhibited inhibitory activity against intracellular ROS generation and cell-damaging effects induced by hydroxyl radicals in a dose-dependent manner. Total phenolic and flavonoid contents were 22.3 mg·g^-1 gallic acid equivalent and 16.2 mg·g^-1 catechin equivalent, respectively. Additionally, a high-performance liquid chromatography (HPLC) assay based on the internal standard method used to detect phenolic compounds. The phenolic compounds identified in C. lanceolata extract contained (+)-catechin hydrate (5.0 ± 0.0 mg·g^-1), ferulic acid (1.6 ± 0.0 mg·g^-1), chlorogenic acid (1.5 ± 0.0 mg·g^-1), caffeic acid (1.2 ± 0.0 mg·g-1), naringin (0.9 ± 0.0 mg·g^-1), and p-coumaric acid (0.5 ± 0.0 mg·g^-1). C. lanceolata extract attenuated pro-apoptotic Bax expression levels and enhanced the expression levels of anti-apoptotic Bcl-2, caspase-3, and caspase-9 proteins. Therefore, C. lanceolata is a potential source of materials with neuroprotective properties against neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.

• Korean Journal of Acupuncture
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• v.41 no.2
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.