• Molecules and Cells
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• v.38 no.1
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• pp.58-64
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• 2015

Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.415-424
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• 2016

Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction.

• Nuclear Engineering and Technology
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• v.54 no.7
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• pp.2475-2490
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• 2022

The Accident Tolerant Fuel (ATF) is a new concept of fuel, which can not only withstand the consequences of the accident for a longer time, but also maintain or improve the performance under operating conditions. ISAA is a self-developed severe accident analysis code, which uses modular structures to simulate the development processes of severe accidents in nuclear plants. The basic version of ISAA is developed based on UO₂-Zr fuel. To study the potential safety gain of ATF cladding, an improved version of ISAA, referred to as ISAA-ATF, is introduced to analyze the station blackout accident of PWR using ATF cladding. The results show that ATF cladding enable the core to maintain a longer time compared to zirconium alloy cladding, thereby enhancing the accident mitigation capability. Meanwhile, the generation of hydrogen is significantly reduced and delayed, which proves that ATF can improve the safety characteristics of the nuclear reactor.

• Molecules and Cells
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• v.41 no.5
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• pp.390-400
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• 2018

Studies have revealed that miR-103a-3p contributes to tumor growth in several human cancers, and high miR-103a-3p expression is associated with poor prognosis in advanced gastric cancer (GC) patients. Moreover, bioinformatics analysis has shown that miR-103a-3p is upregulated in The Cancer Genome Atlas (TCGA) stomach cancer cohort. These results suggest that miR-103a-3p may function as an oncogene in GC. The present study aimed to investigate the role of miR-103a-3p in human GC. miR-103a-3p expression levels were increased in 33 clinical GC specimens compared with adjacent nontumor stomach tissues. Gain- and loss-of-function studies were performed to identify the correlation between miR-103a-3p and tumorigenesis in human GC. Inhibiting miR-103a-3p suppressed GC cell proliferation and blocked the S-G2/M transition in MKN-45/SGC-7901 cells, whereas miR-103a-3p overexpression improved GC cell proliferation and promoted the S-G2/M transition in vitro. Bioinformatics and dual-luciferase reporter assays confirmed that ATF7 is a direct target of miR-103a-3p. Analysis of the TCGA stomach cancer cohort further revealed that miR-103a-3p expression was inversely correlated with ATF7 expression. Notably, silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. ATF7 overexpression eliminated the effects of miR-103a-3p expression. These findings indicate that miR-103a-3p promotes the proliferation of GC cell by targeting and suppressing ATF7 in vitro.

• Korean Journal of Plant Resources
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• v.30 no.5
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• pp.556-564
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• 2017

Appropriate soil temperature and early planting of potato is very important for the successful potato-soybean cropping system in central region of South Korea. This experiment was carried out to determine the effect of mulching materials on the growth and yield of potato (Solanum tuberosum L.). Five different mulch treatments were had been applied on an upland soil as follows ; no mulch (NM), transparent film (TF), transparent film + additional transparent film (TF + ATF), black film (BF), and black film + additional transparent film (ATF). In the period of sowing time to removing additional films, mean soil temperature of the treatments was in the order of TF+ATF > TF > BR+ATF > BF as $20.3^{\circ}C$ > $18.5^{\circ}C$ > $16.1^{\circ}C$ > $15.4^{\circ}C$, respectively and that of NM was $13.8^{\circ}C$. The accumulated soil temperature was TF > NM > BF during the removing additional films to earthing at inter-tillage. On the changes in the soil temperature during a whole day, the temperature in the BF was lower than NM during around 18:00 PM to 12:00 NM, while NM was higher than BF in the time period of 10:00AM to 21:00PM. The sequence of potato sprout emergence was 15 > 18 > 20 > 22 days of TF+ATF, TF, BF+ATF, and BF, respectively and that of NM was 24 days. Comparing to the NM, potato sprout emergence was observed on the TF+ATF treated plot as early as 9 days. At 10 days before harvest, the significant difference in the tuber dry weight had been observed and the sequence tuber weight was in the order of TF > TF+ATF > BF+ATF > BF > NM. The potato yields of TF, TF+ATF, and BF+ATF were increased of 40.7, 37.3, and 22% as compared to NM ($2,805kg\;10a^{-1}$), but almost same yield in the BF. The differences of tuber dry weight and potato yields was co-related with the temperature rise of soil by the application of mulching materials on soil. Based on these results, application of mulching film had been very effective to increase the tuber size and the yield of potato by the temperature rise during seedling stage of potato. Transparent mulching was better than black mulching especially for the emergence of sprout of potato in relation to minimizing cooling injury.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.97-97
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• 2018

Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated $I{\kappa}B-{\alpha}$ degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, $TNF-{\alpha}$, IL-6, $IL-1{\beta}$ and MCP-1 via interruption of the $NF-{\kappa}B$ and MAPK/ATF2 signaling pathways.

• Korean Journal of Plant Resources
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• v.31 no.6
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• pp.612-621
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• 2018

Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated $I{\kappa}B$-${\alpha}$ degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, $TNF-{\alpha}$, IL-6, $IL-1{\beta}$ and MCP-1 via interruption of the $NF-{\kappa}B$ and MAPK/ATF2 signaling pathways.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.65-65
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• 2019

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (LCLE) and branches (LCBE) from L. caerulea in LPS-stimulated RAW264.7 cells. Inhibitory effect of LCLE and LCBE against LPS-induced overproduction of NO, iNOS and $IL-1{\beta}$ was higher than LCFE. Furthermore, LCLE and LCBE significantly inhibited the overexpression of COX-2, IL-6 and $TNF-{\alpha}$ in LPS-stimulated RAW264.7 cells. LCLE and LCBE did not inhibited LPS-induced degradation of $I{\kappa}B-{\alpha}$, but blocked the nuclear accumulation of p65. LCLE did not inhibited LPS-induced phosphorylation of ERK1/2 and p38, while LCBE significantly attenuated phosphorylation level of p38. LCLE and LCBE increased HO-1 protein level and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by HO-1 knockdown. The inhibition of p38 by SB203580 and ROS by NAC blocked HO-1 expression by LCLE and LCBE. LCLE and LCBE increased p38 phosphorylation and the inhibition of ROS by NAC blocked p38 phosphorylation LCLE and LCBE. LCLE and LCBE induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 and ROS. In addition, LCLE and LCBE increased ATF3 expression and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by ATF3 knockdown. Collectively, LCLE and LCBE inhibited LPS-induced $NF-{\kappa}B$ activation by blocking p65 nuclear accumulation, increased HO-1 expression by ROS/p38/Nrf2 activation, and increased ATF3 expression. Furthermore, LCBE inhibited LPS-induced p38 phosphorylation.

• Nuclear Engineering and Technology
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• v.56 no.7
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• pp.2625-2632
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• 2024

In this study, we investigated the possibility of employing accident tolerant fuel (ATF) in VVER-1200/V491 assembly without gadolinium-containing fuel rods using the Monte Carlo code Serpent 1.1.7 with ENDF/B-VII cross-section library. The analysis involves assembly design with reflective boundary conditions. To compare the neutronic performances, U-5Mo, U-7.5Mo, U-10Mo, and U-15Mo fuels were chosen in addition to ordinary UO₂ fuel. The concentration of ¹³⁵Xe, ¹⁴⁹Sm, fissile and fertile isotopes with burnup, reactivity feedback with fuel temperature variation, and β eff values were calculated. The results indicate that the fuel cycle length increases by 54.27% for U-5Mo, 32.6% for U-7.5Mo, and 13.8% for U-10Mo, while it decreases by 16.4% for U-15Mo fuel. Additionally, the effect of ⁹⁵Mo content in natural Mo was investigated by reducing the ⁹⁵Mo concentration. According to the results, each proposed fuel's fuel cycle length extended when the depletion ratio of ⁹⁵Mo increased. Additionally, the calculations for reactivity feedback guarantee safe operating conditions for all U-xMo fuels.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.1-18
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• 2024

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)₂D₃ after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)₂D₃ during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)₂D₃ treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)₂D₃ administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)₂D₃ inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)₂D₃ treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)₂D₃ prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.