• Title/Summary/Keyword: Co-regulator

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miR-7b Promoter Contains Negative Gene Elements (네거티브 유전자 조절인자를 포함하는 마이크로RNA, miR-7b의 프로모터)

  • Choi, Ji-Woong;Lee, Heon-Jin
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1784-1788
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    • 2011
  • The typical miRNA and its nearby host gene are co-expressed by sharing the same promoter. We assumed that miR-7b and its host gene FICT might use an identical promoter for their brain specific gene expression. Sequence comparison of the genomic DNA of mouse miR-7b, human miR-7-3 and their host genes by using the bioinformatic tools revealed high sequence homology and several putative transcription factor-binding sites on the promoter region. In order to probe the hypothesis we used a luciferase vector system into which we cloned the 5' upstream conserved region of miR-7b and FICT. The putative promoter region showed decreased luciferase activity, suggesting that the 5' upstream of miR-7b and FICT contain a negative regulator for gene expression.

Root Bark of Morus Alba Suppresses the YAP Activity through Activation of Classical Hippo Signaling Pathway (상근피의 Hippo 신호전달 경로 활성화를 통한 YAP 억제 효능)

  • Cho, You Na;Choi, Da Bin;Jeong, Han Sol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.4
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    • pp.191-197
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    • 2019
  • This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.

Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism

  • Pantha, Rubee;Lee, Jae-Ho;Bae, Jae-Hoon;Koh, Eun Hee;Shin, Minsang;Song, Dae-Kyu;Im, Seung-Soon
    • BMB Reports
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    • v.54 no.9
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    • pp.476-481
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    • 2021
  • Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1f/f and LRH-1 liver-specific knockout (Lrh-1LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1f/f mice. Interestingly, in the Lrh-1LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting.

MicroRNA-127 promotes antimicrobial ability in porcine alveolar macrophages via S1PR3/TLR signaling pathway

  • Honglei Zhou;Yujia Qian;Jing Liu
    • Journal of Veterinary Science
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    • v.24 no.2
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    • pp.20.1-20.13
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    • 2023
  • Background: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. Objectives: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. Methods: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. Results: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. Conclusions: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.

Subcritical water extraction of Gracilaria chorda abbreviates lipid accumulation and obesity-induced inflammation

  • Laxmi Sen Thakuri;Chul Min Park;Jin Woo Park;Hyeon-A Kim;Dong Young Rhyu
    • ALGAE
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    • v.38 no.1
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    • pp.81-92
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    • 2023
  • Obesity-induced inflammation is crucial in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we investigated the effects of the Gracilaria chorda (GC) on lipid accumulation and obesity-induced inflammatory changes or glucose homeostasis in cell models (3T3-L1 adipocytes and RAW 264.7 macrophages). Samples of GC were extracted using solvents (water, methanol, and ethanol) and subcritical water (SW) at different temperatures (90, 150, and 210℃). The total phenolic content of GCSW extract at 210℃ (GCSW210) showed the highest content compared to others, and GCSW210 highly inhibited lipid accumulation and significantly reduced gene expressions of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein-1c, and fatty acid synthase in 3T3-L1 adipocytes. In addition, GCSW210 effectively downregulated the pro-inflammatory cytokine regulator pathways in RAW 264.7 macrophages, including mitogen-activated protein kinase, signal transducers and activators of transcription and nuclear factor-κB. In co-culture of 3T3-L1 adipocytes and RAW 264.7 macrophages, GCSW210 significantly reduced nitric oxide production and interleukin-6 levels, and improved glucose uptake with dose-dependent manner. These findings suggest that GCSW210 improves glucose metabolism by attenuating obesity-induced inflammation in adipocytes, which may be used as a possible treatment option for managing obesity and associated metabolic disorders.

Harnessing the Power of IL-7 to Boost T Cell Immunity in Experimental and Clinical Immunotherapies

  • Jung-Hyun Park;Seung-Woo Lee;Donghoon Choi;Changhyung Lee;Young Chul Sung
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.9.1-9.21
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    • 2024
  • The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

A Power MOSFET Driver with Protection Circuits (보호 회로를 포함한 전력 MOSFET 구동기)

  • Han, Sang-Chan;Lee, Soon-Seop;Kim, Soo-Won;Lee, Duk-Min;Kim, Seong-Dong
    • Journal of the Korean Institute of Telematics and Electronics D
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    • v.36D no.2
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    • pp.71-80
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    • 1999
  • In this paper, a power MOSFET driver with protection circuits is designed using a 2${\mu}m$ high-voltage CMOS process. For stable operations of control circuits a power managing circuit is designed, and a voltage-detecting short-circuit protection(VDSCP) is proposed to protect a voltage regulator in the power control circuit. The proposed VDSCP scheme eliminates voltage drop caused by a series resistor, and turns off output current under short-circuit state. To protect a power MOSFET, a short-load protection, a gate-voltage limiter, and an over-voltage protection circuit are also designed A high voltage 2 ${\mu}m$ technology provides the breakdown voltage of 50 V. The driver consumes the power of 20 ~ 100 mW along its operation state excluding the power of the power MOSFET. The active area of the power MOSFET driver occupies $3.5 {\times}2..8mm^2$.

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The GABAB receptor associates with regulators of G-protein signaling 4 protein in the mouse prefrontal cortex and hypothalamus

  • Kim, Gyeongwha;Jung, Soonwoong;Son, Hyeonwi;Kim, Sujeong;Choi, Jungil;Lee, Dong Hoon;Roh, Gu Seob;Kang, Sang Soo;Cho, Gyeong Jae;Choi, Wan Sung;Kim, Hyun Joon
    • BMB Reports
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    • v.47 no.6
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    • pp.324-329
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    • 2014
  • Regulators of G-protein signaling (RGS) proteins regulate certain G-protein-coupled receptor (GPCR)-mediated signaling pathways. The GABAB receptor ($GABA_BR$) is a GPCR that plays a role in the stress response. Previous studies indicate that acute immobilization stress (AIS) decreases RGS4 in the prefrontal cortex (PFC) and hypothalamus (HY) and suggest the possibility of a signal complex composed of RGS4 and $GABA_BR$. Therefore, in the present study, we tested whether RGS4 associates with $GABA_BR$ in these brain regions. We found the co-localization of RGS4 and $GABA_BR$ subtypes in the PFC and HY using double immunohistochemistry and confirmed a direct association between $GABA_{B2}R$ and RGS4 proteins using co-immunoprecipitation. Furthermore, we found that AIS decreased the amount of RGS4 bound to $GABA_{B2}R$ and the number of double-positive cells. These results indicate that $GABA_BR$ forms a signal complex with RGS4 and suggests that RGS4 is a regulator of $GABA_BR$.

A study on simulation modeling of the underground space environment-focused on storage space for radioactive wastes (지하공간 환경예측 시뮬레이션 개발 연구-핵 폐기물 저장공간 중심으로)

  • 이창우
    • Tunnel and Underground Space
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    • v.9 no.4
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    • pp.306-314
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    • 1999
  • In underground spaces including nuclear waste repository, prediction of air quantity, temperature/humidity and pollutant concentration is utmost important for space construction and management during the normal state as well as for determining the measures in emergency cases such as underground fires. This study aims at developing a model for underground space environment which has capabilities to take into account the effects of autocompression for the natural ventilation head calculation, to find the optimal location and size of fans and regulators, to predict the temperature and humidity by calculating the convective heat transfer coefficient and the sensible and latent heat transfer rates, and to estimate the pollutant levels throughout the network. The temperature/humidity prediction model was applied to a military storage underground space and the relative differences of dry and wet temperatures were 1.5 ~ 2.9% and 0.6 ~ 6.1%, respectively. The convection-based pollutant transport model was applied to two different vehicle tunnels. Coefficients of turbulent diffusion due to the atmospheric turbulence were found to be 9.78 and 17.35$m^2$/s, but measurements of smoke and CO concentrations in a tunnel with high traffic density and under operation of ventilation equipment showed relative differences of 5.88 and 6.62% compared with estimates from the convection-based model. These findings indicate convection is the governing mechanism for pollutant diffusion in most of the tunnel-type spaces.

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Trinexapac-ethyl Treatment for Kentucky Bluegrass of Golf Course during Summer (하절기 켄터키블루그래스 관리를 위한 식물생장조절제 Trinexapac-ethyl의 활용)

  • Tae, Hyun-Sook;Hong, Beom-Seok;Cho, Yong-Sup;Oh, Sang-Hun
    • Asian Journal of Turfgrass Science
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    • v.24 no.2
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    • pp.156-160
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    • 2010
  • This study was performed to provide useful information for kentucky bluegrass management during summer by application of plant growth regulator, Trinexapac-ethyl. Visual quality, shoot density and chlorophyll contents of treatment blocks were significantly different from those of control during summer by application of Trinexapac-ethyl. The turfgrass density of treatment was increased of 4ea/$10\;cm^2$, especially about 5ea/$10\;cm^2$ during the growth retarded period of June and July. Chlorophyll contents index and visual quality of kentucky bluegrass were improved by application of Trinexapac-ethyl during summer, too. In addition, the occurrence of foliage in rainy and high temperature season was less than that of control. However, there was no significant difference in the root length of Kentucky Bluegrass. Meanwhiles, mowing height of kentucky Bluegrass was suppressed by 38% at 2 WAT week after treatment and that there was no significant growth of treatment at 4 WAT. In this experiment, turfgrass quality was significantly better than that of control during July, even though trinexapac-ethyl wasn't applied at all in July. Consequently, periodic treatment of trinexapac- ethyl from spring would be very important to promote the turfgrass visual quality during summer which is unfavorable season on the growth of kentucky bluegrass. And it is possible to reduce mowing times at least 30% for 2 weeks by one application of Trinexapac-ethyl 0.02~0.03 ml/$m^2$ in kentucky bluegrass fairway. Additively, trinexapac- ethyl treatment can be helpful environmentally by cutting down the fertilizers and pesticides in golf course.