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The Role of ROS-NF-κB Signaling Pathway in Enhancement of Inflammatory Response by Particulate Matter 2.5 in Lipopolysaccharide-stimulated RAW 264.7 Macrophages (RAW 264.7 대식세포에서 지질 다당류에 의한 미세먼지(PM2.5) 유발 염증 반응 증진에 미치는 ROS-NF-κB 신호 전달 경로의 역할)

  • Kwon, Da Hye;Kim, Da Hye;Kim, Min Yeong;Hwangbo, Hyun;Ji, Seon Yeong;Park, Seh-Kwang;Jeong, Ji-Won;Kim, Mi-Young;Lee, Hyesook;Cheong, JaeHun;Nam, Soo-Wan;Hwang, Hye-Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.12
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    • pp.1110-1119
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    • 2021
  • The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (interleukin-6 and -1β) were significantly increased by PM2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.

Fabrication of a Novel Ultra Low Temperature Co-fired Ceramic (ULTCC) Using BaV2O6 and BaWO4 (BaV2O6와 BaWO4을 이용한 초저온 동시소성 세라믹 제조)

  • Kim, Duwon;Lee, Kyoungho
    • Journal of the Microelectronics and Packaging Society
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    • v.28 no.4
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    • pp.11-18
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    • 2021
  • A novel microwave dielectric composite material for ultra-low temperature co-fired ceramics (ULTCC) with (1-x)BaWO4-xBaV2O6 (x=0.54~0.85) composition was prepared by firing a mixture of BaWO4 and BaV2O6. Shrinkage tests showed that the ceramic composite begins to densify at a temperature as low as 550℃ and can be sintered at 650℃ with 98% of relative density under the influence of BaV2O6. X-ray diffraction analysis showed that BaWO4 and BaV2O6 coexisted and no secondary phase was detected in the sintered bodies, implying good chemical compatibility between the two phases. Near-zero temperature coefficients of the resonant frequency (𝛕f) could be achieved by controlling the relative content of the two phases, due to their positive and negative 𝛕f values, respectively. With increasing BaV2O6 (x from 0.53 to 0.85), the 𝛕f value of the composites increased from -7.54 to 14.49 ppm/℃, εr increased from 10.08 to 11.17 and the quality factor (Q×f value) decreased from 47,661 to 37,131 GHz. The best microwave dielectric properties were obtained for x=0.6 samples with εr=10.4, Q×f=44,090 GHz, and 𝛕f=-2.38 ppm/℃. Chemical compatibility experiments showed the developed composites are compatible with aluminum electrode during co-firing process.

Synthesis and Structural Study of Extraframework ZrI6Tl119+ Cationic Cluster in Zeolite A (제올라이트 A 동공 내 비골격 ZrI6Tl119+ 양이온 클러스터의 합성과 구조 연구)

  • Hyeon Seung, Lim;Jong Sam, Park;Cheol Woong, Kim;Woo Taik, Lim
    • Korean Journal of Mineralogy and Petrology
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    • v.35 no.4
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    • pp.447-455
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    • 2022
  • Fully dehydrated Tl12-LTA (|Tl12|[Si12Al12O48]-LTA,Tl12-A) was treated with 6.0×103 Pa of ZrI4 (g) at 623 K for 72 hr under anhydrous conditions. The crystal structure of product, |Zr0.25I1.5Tl12|[Si12Al12O48]-LTA, was determined by single-crystal crystallography using synchrotron X-radiation in the cubic space group Pm3m (a = 12.337(2) Å). It was refined using all data to the final error index (for the 712 unique reflections for which Fo> 4σ(Fo) R1/wR2= 0.055/0.189. In this structure, octahedral ZrI62- ions center about 25% of the large cavities (Zr-I = 2.91(4) Å). Each coordinates to eight Tl+ ions and they are further bridged by Tl+ ions in the planes of 8-rings to form a cubic three-dimensional ZrI6Tl119+ cationic cluster. About 1.5 Tl+ ions per unit cell moved to deeper side of sodalite cavity after reaction with ZrI4(g). The remaining Tl+ ions occupy well-established cation positions near 6- and 8-rings.

CLK3 is a Novel Negative Regulator of NF-κB Signaling (NF-κB 신호경로에서 CLK3의 새로운 음성 조절자로서의 기능)

  • Byeol-Eun, Jeon;Chan-Seong, Kwon;Ji-Eun, Lee;Ye-Lin, Woo;Sang-Woo, Kim
    • Journal of Life Science
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    • v.32 no.11
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    • pp.833-840
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    • 2022
  • Chronic inflammation has been shown to be closely associated with tumor development and progression. Nuclear factor kappa B (NF-κB) is composed of a family of five transcription factors. NF-κB signaling plays a crucial role in the inflammatory response and is often found to be dysregulated in various types of cancer, making it an attractive target in cancer therapeutics. In this study, CDC-like kinase 3 (CLK3) was identified as a novel kinase that regulates the NF-κB signaling pathway. Our data demonstrate that CLK3 inhibits the canonical and non-canonical NF-κB pathways. Luciferase assays following the transient or stable expression of CLK3 indicated that this kinase inhibited NF-κB activation mediated by Tumor necrosis factor-alpha (TNFα) and Phorbol 12-myristate 13-acetate (PMA), which are known to activate NF-κB signaling via the canonical pathway. Consistent with data on the ectopic expression of CLK3, CLK3 knockdown using shRNA constructs increased NF-κB activity 1.5-fold upon stimulation with TNFα in HEK293 cells compared with the control cells. Additionally, overexpression of CLK3 suppressed the activation of this signaling pathway induced by NF-κB-inducing kinase (NIK) or CD40, which are well-established activators of the non-canonical pathway. To further examine the negative impact of CLK3 on NF-κB signaling, we performed Western blotting following the TNFα treatment to directly identify the molecular components of the NF-κB pathway that are affected by this kinase. Our results revealed that CLK3 mitigated the phosphorylation/activation of transforming growth factor-α-activated kinase 1 (TAK1), inhibitor of NF-κB kinase alpha/beta (IKKα/α), NF-κB p65 (RelA), NF-κB inhibitor alpha (IκBα), and Extracellular signal-regulated kinase 1/2-Mitogen-activated protein kinase (ERK1/2-MAPK), suggesting that CLK3 inhibits both the NF-κB and MAPK signaling activated by TNFα exposure. Further studies are required to elucidate the mechanism by which CLK3 inhibits the canonical and non-canonical NF-κB pathways. Collectively, these findings reveal CLK3 as a novel negative regulator of NF-κB signaling.

Effect of Natural Product Extracts on Inhibition of Macrophage and Basophil (천연물 추출물이 대식세포 및 호염구 활성 억제에 미치는 영향)

  • Park, Jaehyun;Jang, Jimin;Cha, Sang-Ryul;Baek, Hyosin;Lee, Jooyeon;Lee, You-Hui;Ryu, Semin;Yang, Se-Ran
    • Journal of Food Hygiene and Safety
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    • v.37 no.3
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    • pp.189-197
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    • 2022
  • Asthma is a chronic inflammatory disease characterized by recurring symptoms, airflow obstruction, and bronchial hyper-responsiveness. The onset of asthma for most patients begins early in life, and current asthma treatment with anti-inflammatory agents can have adverse effects, eventually leading to impaired quality of life. In the pathogenesis of asthma, macrophages and basophils play a vital role during progression. Macrophages not only induce inflammation by secreting inflammatory cytokines but also promote DNA damage and mucus production through nitric oxide (NO) production. Basophils enhance eosinophil recruitment and aggravate asthma through the FcεRIα receptor with high affinity for histamine and IgE. Therefore, in this study, we investigated whether the activation of macrophages and basophils is suppressed by the individual extracts of 28 natural products. RAW 264.7 cells (mouse macrophages) were treated with the natural products in LPS, and 4 natural product extracts resulted in decreased NO production. In β-hexosaminidase assay using RBL-2H3 cells (rat basophils), 19 natural product extracts decreased β-hexosaminidase production. In NO production and β-hexosaminidase assay using macrophages and basophils, 3 natural product extracts (Plantago asiatica, Centella asiatica, and Perilla frutescens var. japonica) significantly inhibited NO production and β-hexosaminidase release. Overall, we examined the inhibitory effects of 28 natural product extracts on macrophage and basophil activity, and the findings demonstrated the potential of natural product extracts for treating asthma and macrophage- and basophil-related diseases.

Immune-enhancing and Anti-inflammatory Effects of HK Shiitake Mushroom Mycelium (HKSMM) using Balb/c Mice (Balb/c 마우스를 이용한 HK 표고버섯 균사체(HKSMM)의 면역증강 및 항염효과)

  • Kim, Hun Hwan;Ha, Sang Eun;Park, Min Young;Jeong, Se Hyo;Bhagwan, Bhosale Pritam;Abuyaseer, Abusaliya;Kim, Jeong Ok;Ha, Yeong Lae;Kim, Gon Sup
    • Journal of Life Science
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    • v.32 no.6
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    • pp.447-454
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    • 2022
  • In this study, we confirmed the effect of HK shiitake mushroom mycelium (HKSMM) on immune enhancement in Balb/c mice. Experimental animals were divided into five groups: negative control (NC), positive control (PC; 1,000 mg/100 g; AHCC), T1 (500 mg/100 g; HKSMM), T2 (1,000 mg/100 g; HKSMM), and T3 (2,000 mg/100 g; HKSMM), and dissection was performed at four and six weeks. COX-2 and iNOS concentrations were significantly lower in the six-week experimental group than in the control group, and the NO results were also similar. Results of the confirmation of the factors related to the NF-κB (p-p65 and p-IκBα) and MAPK (pERK, pJNK, and p38) signaling pathways revealed that the HKSMM-fed experimental group significantly decreased compared with the control group. A comparative analysis of the number and size of white pulp in the spleen tissue showed that those of the experimental group were significantly higher than those of the control group in a concentration-dependent manner. These results suggest that HKSMM has both immune-enhancing and anti-inflammatory effects in Balb/c mice, indicating that it can be used as a health functional food ingredient.

Effect on Physiological Metabolism of Calcium Ion at Cell Membrane Model of Parathyroid which Irradiated by High Energy X-ray (고에너지 엑스선을 조사한 부갑상선의 세포막모델에서 칼슘이온의 생리학적 대사에 미치는 영향)

  • Ko, In-Ho;Yeo, Jin-Dong
    • Journal of the Korean Society of Radiology
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    • v.16 no.2
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    • pp.141-150
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    • 2022
  • The initial co-transport and counter-transport permeate transport characteristics of calcium ion at epithelial cell membrane model in parathyroid which irradiated by high energy x-ray(linac 6 MV) was investigated. The epithelial cell membrane model used in this experiment was a polysulfonated copolymerized membrane of poly(PS-DVB: polystyrene-divinylbenzene). The difference of sorbed water in membrane, fixed carrier concentration(SO32-), initial pH value, OH- concentration were occurred at difference of Ca2+concentration and quantity of parathyroid hormone, respectively. The initial co-transport and counter-transport permeate flux of Cl-, OH-, Ca2+ on fixed carrier concentration(SO32-) and initial pH value of irradiated membrane was found to be decreased than non-irradiated membrane. The initial co-transport and counter-transport permeate flux of Ca2+ on fixed carrier concentration (SO32-), initial pH value, OH- concentration in irradiated membrane were found to be decreased about 2.68 ~ 6.87 times, about 1.42 ~ 1.63 times, about 2.07 ~ 1.672 times than non-irradiated membrane, respectively. As a result, the quantity of parathyroid hormone was decreased at irradiated membrane than non-irradiated membrane. The decrease of parathyroid hormone was occurred at hypoparathyroidism and osteoporosis, parathyroiditis, and so on. As the parathyroid hormone in epithelial cell membrane model were abnormal, cell damages were appeared at cell.

The Decreased Expression of Fbxw7 E3 Ligase Mediated by Cancer Upregulated Gene 2 Confers Cancer Stem Cell-like Phenotypes (CUG2 유전자에 의하여 감소된 FBXW7 E3 ligase 발현이 유사-종양줄기세포 표현형을 유도)

  • Yawut, Natpaphan;Kim, Namuk;Budluang, Phatcharaporn;Cho, Il-Rae;Kaowinn, Sirichat;Koh, Sang Seok;Kang, Ho Young;Chung, Young-Hwa
    • Journal of Life Science
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    • v.32 no.4
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    • pp.271-278
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    • 2022
  • The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

A Review on Ocean Acidification and Factors Affecting It in Korean Waters (우리나라 주변 바다의 산성화 현황과 영향 요인 분석)

  • Kim, Tae-Wook;Kim, Dongseon;Park, Geun-Ha;Ko, Young Ho;Mo, Ahra
    • Journal of the Korean earth science society
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    • v.43 no.1
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    • pp.91-109
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    • 2022
  • The ocean is a significant sink for atmospheric anthropogenic CO2, absorbing one-third of the total CO2 emitted by human activities. In return, oceans have experienced significant declines in seawater pH and the aragonite saturation state also called ocean acidification. This study evaluates the distribution of aragonite saturation state, an indicator to assess the potential threat from ocean acidification, by combining newly obtained data from the west coast of South Korea with previous datasets covering the Yellow Sea, East Sea, northern South China Sea, and southeast coast of South Korea. In general, offshore waters absorb atmospheric CO2; however, most of the collected water samples show aragonite oversaturation. On the southeast coast, the aragonite saturation state was significantly affected by river discharge and associated variables, such as freshwater input with nutrients, seasonal stratification, biological carbon fixation, and bacterial remineralization. In summer, hypoxia and mixing with relatively acidic freshwater made the Jinhae and Gwangyang Bays undersaturated with respect to aragonite, possibly threatening marine organisms with CaCO3 shells. However, widespread aragonite undersaturation was not observed on the west coast, which receives considerable river water discharge. In addition, occasional upwelling events may have worsened the ocean acidification in the southwestern part of the East Sea. These results highlight the importance of investigating site-specific ocean acidification processes in coastal waters. Along with the above-mentioned seasonal factors, the dissolution of atmospheric CO2 and the deposition of atmospheric acidic substances will continue to reduce the aragonite saturation state in Korean waters. To protect marine ecosystems and resources, an ocean acidification monitoring program should be established for Korean waters.

Study of the Difference in Residual Amounts according to the Method of Securing Intravenous Injections and the Dose of Physiological Saline during 18F-FDG Administration (18F-FDG 투여 시 정맥주사 확보 방법 및 생리식염수 용량에 따른 잔류량의 차이에 관한 연구)

  • Ryu, Chan-Ju
    • Journal of the Korean Society of Radiology
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    • v.16 no.2
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    • pp.95-102
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    • 2022
  • This study compares the difference between the remaining amount in syringes according to injection method and the dose of physiological saline when the radiopharmaceutical 18F-FDG isotope is injected into patients who visited the hospital for PET examination. After performing a CT or MRI using a contrast medium when 18F-FDG was injected into 40 patients who came to the hospital for PET examination without removing the 3-way, the radioactivity remaining in the syringe and the 3-way was measured and the dose of radioactivity confirmed. At this time, 20 patients were divided into different dose groups of physiological saline. Another injection method was used to compare the remaining amount of the syringe and the difference in the remaining amount according to the amount of physiological saline when the injection was performed with an extension. After an injection of 18F-FDG, the actual administered dose was confirmed by measuring the radioactivity remaining in the syringe and the 3-way or extension with a calibrator. As a result of measuring the radioactivity of the syringe before administering the radiopharmaceutical and the radioactivity of the syringe and the 3-way or extension after administration, the 3-way injection method in 10 cc's of physiological saline had the lowest residual amount. The remaining amount increased in the order of the extension to 10 cc's of saline and the 3-way to 5 cc's of saline. Likewise, the 5 cc's saline solution and the extension injection method demonstrated the highest residual amounts. The residual difference with the lowest level of remaining injection method was found to be 0.053 mCi. It was found that in a PET examination, by considering the radioactivity remaining in the 3-way and extension and by adjusting the dose of physiological saline, if the intended dose to be administered to the actual patient is determined, it is possible to administer the radiopharmaceutical to the patient more accurately.