• Molecules and Cells
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• 제38권1호
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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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• 제20권4호
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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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• 제54권7호
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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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• 제41권5호
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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.

• 한국자원식물학회지
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• 제30권5호
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• pp.556-564
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• 2017

중부지역에서 감자와 콩의 안전다수확 작부체계를 위해서는 전작물인 봄감자의 조기 파종과 초기생육을 위한 적정 토양 온도의 확보가 결정적 요인으로 작용한다. 따라서 본 실험은 비닐 피복의 종류별 지온상승효과와 이에 따른 감자의 생육과 수량에 미치는 영향을 검토하였다. 봄감자 초기생육기간인 파종부터 덧 필름 제거 시까지 처리구별 평균지온은 무피복구(NM) $13.8^{\circ}C$에 비하여 투명필름+덧 필름 > 투명필름 > 흑색필름+덧 필름 > 흑색필름 순으로 각각 $20.3^{\circ}C$ > $18.5^{\circ}C$ > $16.1^{\circ}C$ > $14.5^{\circ}C$ 높았다. 일중 시간대별 온도변화를 보면, 기온이 낮은 오후 6~9시부터 익일 오전 11~12시까지는 BF의 지온이 NM보다 낮았던 반면, 기온이 높은 오전 10~12시부터 오후 6~9시까지는 NM의 지온이 BF의 지온보다 높았다. 감자 싹의 지상부 출현은 TF+ATF > TF > BF+ATF > BF 순으로 각각 15일 > 18일 > 20일 > 22일 빨랐으며, TF+ATF 처리구의 경우 무처리구(NM) 24일에 비하여 무려9일 이나 빨리 감자 싹이 출현되었다. 수확 10일 전 처리구간 감자 지하부 건물중 차이는 TF > TF+ATF > BF+ATF > BF > NM 순이었으며, 통계적으로 유의성 있게 높았다. 이는 처리구별 지온상승효과와 거의 일치하였다. 감자 수량은 대조구인 NM 처리의 $2,805kg\;10a^{-1}$ 비하여 TF에서 41%, TF+ATF 처리는 37% 및 BF+ATF 처리는 2% 증수되었고, BF 처리는 유사하였다. 본 실험은 비닐피복으로 지온을 높여 생육을 증진시키고자 하는데 목표가 있었다. 본 실험의 결과 봄감자 안전다수확 재배를 위해서는 생육초기 지온상승과 생육촉진효과가 높고 조기파종과 출현을 촉진하여 보다 긴 생육기간을 확보 할 수 있는 투명필름 피복이 효과적이고, 덧 필름 피복은 기상조건에 따라 경제성을 고려하여 선택을 하는 것이 좋은 것으로 판단되어진다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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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.

• 한국자원식물학회지
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• 제31권6호
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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.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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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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• 제56권7호
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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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• 제18권1호
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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.