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Regulation of tumor-associated macrophage (TAM) differentiation by NDRG2 expression in breast cancer cells

  • Lee, Soyeon;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • BMB Reports
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    • v.55 no.2
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    • pp.81-86
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    • 2022
  • Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

Comparison in Anthesis Characterics of Some Male Sterile Rice Cultivars (수도 웅성불임계통의 개화특성 비교)

  • Suh, Hak-Soo;Cho, Young-Chan;Park, Tae-Seok
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.30 no.4
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    • pp.427-430
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    • 1985
  • Extrusion degree of stigma, numbers of opened florets at different time during anthesis, angle of opening florets and outcrossed seed set percent were investigated in four male sterile rices having background of Korean cultivars; Suwon 296A, Suwon 304A, Suwon 310A and Suwon 296GMS, and the Chinese cytoplasmic genetic male sterile rice Zhenshan 97A as control in order to get basic informations for hybrid rice breeding. The results obtained were summarized as follows; Extrusion degree of stigma in the four Korean male sterile lines tested was lower than in the Chinese one Zhenshan 97A. The better extrusion of stigma showed the higher outcross rate in male sterile rices. There were almost no relationships between peak of anthesis and outcrossed seed set in the male sterile rices tested. Large anthesis angle with long anthesis duration appeared to be essential for high outcrossed seed set of the male sterile rices. The genetic male sterile line showed the larger anthesis angle than the cytoplasmic and genetic male sterile one in the lines having the same background to the Korean rice cultivar Suwon 296.

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TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells

  • Zahra Zandieh;Azam Govahi;Azin Aghamajidi;Ehsan Raoufi;Fatemehsadat Amjadi;Samaneh Aghajanpour;Masoomeh Golestan;Reza Aflatoonian
    • Clinical and Experimental Reproductive Medicine
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    • v.50 no.1
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    • pp.44-52
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    • 2023
  • Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Evaluation of Hand-Arm Vibration Exposure Level and Work Environment Satisfaction of Workers in Automobile Manufacturer Assembly Process (자동차 제조업체 조립공정 근로자의 국소진동 노출 수준 및 작업환경 만족도 평가)

  • Seong-Hyun Park;Mo-Yeol Kang;Seung Won Kim;Sangjun Choi
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.33 no.2
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    • pp.103-114
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    • 2023
  • Objectives: This study was conducted to evaluate hand-arm vibration (HAV) exposure levels due to the use of power hand tools and to evaluate the determinants in the automobile assembly process. Methods: The exposure level to HAV was evaluated for 30 work lines in five assembly processes (body, engine, chassis, door, and design) that use air-powered tools and battery-powered tools and operate in circulation for two hours. The 2-hr equivalent energy vibration acceleration, A (2), of the task was measured. The 8-hr equivalent energy vibration acceleration, A (8), was estimated in consideration of the number of tasks that can be performed per day by each process. In addition, a survey on the working environment was conducted with workers exposed to vibration. Results: The geometric mean of the HAV exposure level, A (2), for a total of 30 tasks was 2.51 m/s2, and one case was 10.30 m/s2, exceeding TLV (2hr). The HAV exposure level of A (8) was evaluated from 1.03 m/s2 to 5.36 m/s2. A (2) showed a statistically significant difference (P<0.01) for each process, and the chassis process (GM=3.90 m/s2) was the highest. The larger the tool size and the longer the tool length, the higher was the vibration acceleration when using a battery-powered tool than an air-powered tool (P<0.01). Battery-powered tool users showed higher dissatisfaction on all items than did air-powered tool users. Conclusions: As a result of this study, it is necessary to implement a program to reduce the HAV exposure levels.

Study on the Growth and Flowering Characteristics according to the Sowing Time of Genetic Resources of Cruciferae (십자화과(Cruciferae) 유전자원의 파종시기에 따른 생육 및 개화특성 조사)

  • Kwang-Soo Kim;Da-Eun Kwon;Ji-Eun Lee;Young-Lok Cha;Yong-Ku Kang
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.08a
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    • pp.52-52
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    • 2020
  • 유채(Brassica napus L.)는 식용유 생산을 목적으로 재배되며, 1975년에는 26.8천ha가 재배되어 연간 생산량이 34.7천톤이 생산되었으나, 외국으로부터 값싼 식용유의 대량수입으로 재배면적이 급격하게 감소되었다. 그러나 최근에 지방자치단체를 중심으로 경관용 재배면적이 증가하고 있고, 건강에 대한 관심이 높아짐에 따라 국내산 non-GM 식용유 생산을 목적으로 유채 재배면적이 급격하게 증가하고 있다. 유채의 대량생산을 위해서는 논 재배가 필수적이나 유채와 벼의 이모작 재배 시기가 겹치는 문제점이 발생하고 있어 조생종 유채의 품종개발과 함께 봄 파종이 가능한 유채의 품종 육성에 대한 요구가 매우 높다. 따라서 본 연구에서는 국내 보유 유채를 포함하는 십자화과(Cruciferae) 유전자원의 특성 평가를 통해 극조숙 유채 품종 육성을 조기에 육성하기 위해 실시하였다. 농촌진흥청 국립유전자원센터에서 분양받은 유전자원 146계통을 파종 재배하면서 핵형분석과 외부형질을 기준으로 정확한 종을 동정하였고, 각 유전자원의 생육 및 개화특성을 조사하였다. 유전자원들을 세포분석기를 이용하여 핵형을 분석한 결과, 전체 146개의 유전자원 중 유채(B. napus L.) 128계통, 갓(B. juncea Sinsk) 6계통, 배추(B. campestris Makino) 9계통, 미분류 3계통 등으로 조사되었다. 유전자원을 가을 파종(10월 22일)하였을 때 개화가 가장 빠른 계통(IT 279089)이 파종 후 137일 이후인 3월7일부터 개화가 시작되었고, 가장 늦은 계통(IT 279198)은 191일 후인 4월 30일에 개화가 시작되었다. 봄 파종(2월 4일)하였을 때 개화가 가장 빠른 계통(IT 279089)이 파종 후 79일 이후인 4월 23일부터 개화가 시작되었고 IT 279092 등 29계통은 추대와 개화가 되지 않았다. 위와 같은 연구결과를 토대로 개화시기가 빠른 유전자원을 육종을 위한 인공교배 시화분친이나 종자친으로 이용하면 지방산 품질이 좋고 극조숙성인 유채 품종의 개발이 가능할 것으로 생각된다.

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Improvement of GOCI-II Ground System for Monitoring of Level-1 Data Quality (천리안 해양위성 2호 Level-1 영상의 품질관리를 위한 지상국 시스템 개선)

  • Sun-Ju Lee;Kum-Hui Oh;Gm-Sil Kang;Woo-Chang Choi;Jong-Kuk Choi;Jae-Hyun Ahn
    • Korean Journal of Remote Sensing
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    • v.39 no.6_2
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    • pp.1529-1539
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    • 2023
  • The data from Geostationary Ocean Color Imager-II (GOCI-II), which observes the color of the sea to monitor marine environments, undergoes various correction processes in the ground station system, producing data from Raw to Level-2 (L2). Quality issues arising at each processing stage accumulate step by step, leading to an amplification of errors in the satellite data. To address this, improvements were made to the GOCI-II ground station system to measure potential optical quality and geolocation accuracy errors in the Level-1A/B (L1A/B) data. A newly established Radiometric and Geometric Performance Assessment Module (RGPAM) now measures five optical quality factors and four geolocation accuracy factors in near real-time. Testing with GOCI-II data has shown that RGPAM's functions, including data processing, display and download of measurement results, work well. The performance metrics obtained through RGPAM are expected to serve as foundational data for real-time radiometric correction model enhancements, assessment of L1 data quality consistency, and the development of reprocessing strategies to address identified issues related to the GOCI-II detector's sensitivity degradation.

GOCI-IIVisible Radiometric Calibration Using Solar Radiance Observations and Sensor Stability Analysis (GOCI-II 태양광 보정시스템을 활용한 가시 채널 복사 보정 개선 및 센서 안정성 분석)

  • Minsang Kim;Myung-Sook Park;Jae-Hyun Ahn;Gm-Sil Kang
    • Korean Journal of Remote Sensing
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    • v.39 no.6_2
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    • pp.1541-1551
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    • 2023
  • Radiometric calibration is a fundamental step in ocean color remote sensing since the step to derive solar radiance spectrum in visible to near-infrared wavelengths from the sensor-observed electromagnetic signals. Generally, satellite sensor suffers from degradation over the mission period, which results in biases/uncertainties in radiometric calibration and the final ocean products such as water-leaving radiance, chlorophyll-a concentration, and colored dissolved organic matter. Therefore, the importance of radiometric calibration for the continuity of ocean color satellites has been emphasized internationally. This study introduces an approach to improve the radiometric calibration algorithm for the visible bands of the Geostationary Ocean Color Imager-II (GOCI-II) satellite with a focus on stability. Solar Diffuser (SD) measurements were employed as an on-orbit radiometric calibration reference, to obtain the continuous monitoring of absolute gain values. Time series analysis of GOCI-II absolute gains revealed seasonal variations depending on the azimuth angle, as well as long-term trends by possible sensor degradation effects. To resolve the complexities in gain variability, an azimuth angle correction model was developed to eliminate seasonal periodicity, and a sensor degradation correction model was applied to estimate nonlinear trends in the absolute gain parameters. The results demonstrate the effects of the azimuth angle correction and sensor degradation correction model on the spectrum of Top of Atmosphere (TOA) radiance, confirming the capability for improving the long-term stability of GOCI-II data.

Clinical Implications of Focal Mineral Deposition in the Globus Pallidus on CT and Quantitative Susceptibility Mapping of MRI

  • Hyojin Kim;Jinhee Jang;Junghwa Kang;Seungun Jang;Yoonho Nam;Yangsean Choi;Na-young Shin;Kook-Jin Ahn;Bum-soo Kim
    • Korean Journal of Radiology
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    • v.23 no.7
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    • pp.742-751
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    • 2022
  • Objective: To assess focal mineral deposition in the globus pallidus (GP) by CT and quantitative susceptibility mapping (QSM) of MRI scans and evaluate its clinical significance, particularly cerebrovascular degeneration. Materials and Methods: This study included 105 patients (66.1 ± 13.7 years; 40 male and 65 female) who underwent both CT and MRI with available QSM data between January 2017 and December 2019. The presence of focal mineral deposition in the GP on QSM (GPQSM) and CT (GPCT) was assessed visually using a three-point scale. Cerebrovascular risk factors and small vessel disease (SVD) imaging markers were also assessed. The clinical and radiological findings were compared between the different grades of GPQSM and GPCT. The relationship between GP grades and cerebrovascular risk factors and SVD imaging markers was assessed using univariable and multivariable linear regression analyses. Results: GPCT and GPQSM were significantly associated (p < 0.001) but were not identical. Higher GPCT and GPQSM grades showed smaller gray matter (p = 0.030 and p = 0.025, respectively) and white matter (p = 0.013 and p = 0.019, respectively) volumes, as well as larger GP volumes (p < 0.001 for both). Among SVD markers, white matter hyperintensity was significantly associated with GPCT (p = 0.006) and brain atrophy was significantly associated with GPQSM (p = 0.032) in at univariable analysis. In multivariable analysis, the normalized volume of the GP was independently positively associated with GPCT (p < 0.001) and GPQSM (p = 0.002), while the normalized volume of the GM was independently negatively associated with GPCT (p = 0.040) and GPQSM (p = 0.035). Conclusion: Focal mineral deposition in the GP on CT and QSM might be a potential imaging marker of cerebral vascular degeneration. Both were associated with increased GP volume.

Change of Dendritic Cell Subsets Involved in Protection Against Listeria monocytogenes Infection in Short-Term-Fasted Mice

  • Young-Jun Ju;Kyung-Min Lee;Girak Kim;Yoon-Chul Kye;Han Wool Kim;Hyuk Chu;Byung-Chul Park;Jae-Ho Cho;Pahn-Shick Chang;Seung Hyun Han;Cheol-Heui Yun
    • IMMUNE NETWORK
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    • v.22 no.2
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    • pp.16.1-16.20
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    • 2022
  • The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103+CD11b- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103+CD11b- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103+CD11b- DCs in mice infected with LM might affect to increase of Foxp3+ regulatory T cells. Changes of major subset of DCs from CD103+ to CD103- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

Inflammatory Reponse of the Lung to Hypothermia and Fluid Therapy after Hemorrhagic Shock in Rats (흰쥐에서 출혈성 쇼크 후 회복 시 저체온법 및 수액 치료에 따른 폐장의 염증성 변화)

  • Jang, Won-Chae;Beom, Min-Sun;Jeong, In-Seok;Hong, Young-Ju;Oh, Bong-Suk
    • Journal of Chest Surgery
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    • v.39 no.12 s.269
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    • pp.879-890
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    • 2006
  • Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.