• Title/Summary/Keyword: regulatory factor

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Oldenlandia diffusa Ameliorates on Atopic Dermatitis in Mice

  • Mi-Ok Yang;Noh-Yil Myung
    • Korean Journal of Plant Resources
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    • v.36 no.6
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    • pp.556-561
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    • 2023
  • Oldenlandia diffusa (OD), a member of the Rubiaceae family, has been used for treating inflammatory and infectious diseases. However, the anti-atopic effects of OD are not completely understood yet. Thus, the aim of the present study was to elucidate beneficial effects of OD on atopic dermatitis (AD) in vivo. We examined the pharmacological effects of OD on compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlrobenzene (DNCB)-induced AD-like skin lesions in mice. Additionally, we evaluated regulatory effects of OD on the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in DNCB-induced AD-like skin lesions. Results showed that OD inhibited the scratching behavior and AD symptoms. It also decreased serum levels of IgE and histamine in mice. Moreover, OD significantly ameliorated the expression of IL-6 and TNF-α in AD-like skin lesion. These finding suggest experimental evidence of that OD's potential for treating AD.

miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon;Kang, Youn-Jung;Kwon, Jinie;Nishi, Yoshihiro;Yanase, Toshihiko;Lee, Kyung-Ah;Koong, Mi Kyoung
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.3
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    • pp.194-206
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    • 2020
  • Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

The Effects of Innovation and Relationship Factors of ASP Service on Customer Performance - Focused on the Regulatory Impact of Supplier Trust (ASP 서비스의 혁신특성과 관계특성이 고객성과에 미치는 효과 - 공급사 신뢰의 조절효과 중심으로)

  • Choi, Dong-Suong;Yi, Seon-Gyu
    • Journal of Digital Convergence
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    • v.16 no.2
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    • pp.169-178
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    • 2018
  • The purpose of this study is to analyze the effect of innovation factors and relationship factors ASP service on customer performance for small firms using ASP service and Supplier trust analyzed the regulatory impact of the innovation factors and relationships factors on customer performance. Sample data was collected using questionnaire techniques, and statistical analysis used regression analysis. As a result of analysis, it is analyzed that the relative advantage of innovation factors and the influence of other companies have a positive effect on customer performance. In the relationship factors, the degree of information sharing was analyzed as a variable that positively influenced customer performance. However, the Flexibility of participants was analyzed as a variable that did not positively affect customer performance. As a result of analyzing the regulatory role of supplier trust, supplier trust is analyzed as a variable that plays a moderating role in customer performance along with innovation factors and relationship factors. Therefore, in the case of small enterprises using ASP service, it was found that innovation factors and information sharing factors are important factor to maximize customer performance. And that the trust of ASP vendors is a very important variable for customers.

The Existence of a Putative Regulatory Element in 3'-Untranslated Region of Proto-oncogene HOX11's mRNA

  • Li, Yue;Jiang, Zhao-Zhao;Chen, Hai-Xu;Leung, Wai-Keung;Sung, Joseph J.Y.;Ma, Wei-Jun
    • BMB Reports
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    • v.38 no.4
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    • pp.500-506
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    • 2005
  • HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5'-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative cis-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3'-untranslated region (3'UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3'UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3'UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3'UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3'UTR, the interaction of HOX11 mRNA 3'UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3'UTR contains cis-acting element which shares similarity in the action pattern with RE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.

Regulatory Effect of Gigukjihwangtanggami on Cytokine Production in Patients with Cerebral Infarction

  • Lee, Min-Goo;Park, Sae-Wook;Lee, Sun-Woo;Son, Ji-Woo;Kang, Baek-Gyu;Park, Sang-Moo;Lee, In;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.1044-1050
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    • 2006
  • The Korean genuine medicine, 'Gigukjihwangtanggami (GJT)' has long been used clinically for hypertension and various cerebrovascular diseases. However, experimental study has been carried out very little. Recently cytokines involved in the regulation of inflammatory reactions and immune responses may play an important role in the pathogenesis of cerebral infarction (CI). The aim of this study is to investigate the effect of GJT on the production of pro-inflammatory cytokines and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCS) stimulated with lipopolysaccaride (LPS) from Cl patients. The amount of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interleukin-1{\beta}\;(IL-1{\beta})$, IL-6, IL-8, IL-4 and IL-10 in PBMC culture supernatant was significantly increased in the LPS treated cells compared to unstimulated cells. GJT inhibited the production of $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 induced by LPS. The maximal inhibition rate of the $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 production by pretreatment of GJT (1 mg/ml) was $57.32{\pm}2.5%$ (p.0.05), $42.02{\pm}3.5%$ (p.0.05), $40.02{\pm}2.3%$ (p.0.05) and $48.02{\pm}3.1$, (p.0.05), respectively. In the Other hand, GJT increased the production of IL-4 and IL-10. The maximal increase rate of the IL-4 and IL-10 production by pretreatment of GJT (1 mg/ml) was $42.4{\pm}3.3%$ (p.0.05) End $56.4{\pm}2.9%$ (p.0.05), respectively. Taken together, these results indicate that GJT Ray have regulatory effects on the cytokine production and suggest that GJT might use clinically for the treatment of CI.

CD206+ dendritic cells might be associated with Heat-pattern and induced regulatory T cells after treatment with bee venom

  • Jung, Woo-Sang;Kwon, Seungwon;Yang, Jung Yun;Jin, Chul;Cho, Seung-Yeon;Park, Seong-Uk;Moon, Sang-Kwan;Park, Jung-Mi;Ko, Chang-Nam;Bae, Hyunsu;Cho, Ki-Ho
    • The Journal of Korean Medicine
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    • v.43 no.2
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    • pp.1-7
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    • 2022
  • Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson's disease, that phospholipase A2 (PLA2) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206+ DCs and clinical syndrome differentiation in TEAM. Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO2 incubator for 72 h. Results: We divided the subjects into a relatively high CD206+ group or a relatively low CD206+ group. The heat factor scores of high CD206+ group were significantly higher than that of low CD206+ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA2, Tregs increased in the high CD206+ group but decreased in the low CD206+ group. Conclusion: In this study, we reconfirm that CD206+ DCs induced Treg differentiation by incubating human blood samples with PLA2 and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA2 therapy because its score was elevated in the high CD206+ group.

Carpomitra costata Extract Alleviates Lipopolysaccharide-induced Neuroinflammatory Responses in BV2 Microglia through the Inactivation of NF-κB Associated with the Blockade of the TLR4 Pathway and ROS Generation

  • Park, Cheol;Cha, Hee-Jae;Hong, Su-Hyun;Kim, Suhkmann;Kim, Heui-Soo;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.12 no.1
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    • pp.29-39
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    • 2020
  • In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

The regulatory mechanism of insulin like growth factor secretion by high glucose in mesangial cell: involvement of cAMP (Mesangial 세포에서 고포도당에 의한 insulin-like growth factor의 분비조절기전에 관한 연구: cAMP와의 관련성)

  • Heo, Jung-sun;Kang, Chang-won;Han, Ho-jae;Park, Soo-hyun
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.563-571
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    • 2003
  • Dysfunction of mesangial cells has been contributed to the onset of diabetic nephropathy. Insulin like growth factors (IGFs) are also implicated in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion in the mesangial cells. Furthermore, the relationship between cAMP and high glucose on the secretion of IGFs was not elucidated. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. Glucose increased IGF-I secretion in a time- (>8 hr) and dose- (>15 mM) dependent manner (p<0.05). Stimulatory effect of high glucose on IGF-I secretion is predominantly observed in 25 mM glucose (high glucose), while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. High glucose also increased IGF-II secretion. The increase of IGF-I and IGF-II secretion is not mediated by osmotic effect, since mannitol and L-glucose did not affect IGF-I and IGF-II secretion. 8-Br-cAMP mimicked high glucose-induced secretion of IGF-I and IGF-II. High glucose-induced stimulation of IGF-I and IGF-II secretion was blocked not by pertussis toxin but by SQ 22536 (adenylate cyclase inhibitor). Rp-cAMP (cAMP antagonist), and myristoylated protein kinase A (PKA) inhibitor amide 14-22 (protein kinase A inhibitor). These results suggest that cAMP/PKA pathways independent of Gi protein may mediate high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. Indeed, glucose (>15 mM glucose) increased cAMP formation. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via cAMP/PKA pathway in mesangial cells.

Effect of critical flow model in MARS-KS code on uncertainty quantification of large break Loss of coolant accident (LBLOCA)

  • Lee, Ilsuk;Oh, Deogyeon;Bang, Youngseog;Kim, Yongchan
    • Nuclear Engineering and Technology
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    • v.52 no.4
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    • pp.755-763
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    • 2020
  • The critical flow phenomenon has been studied because of its significant effect for design basis accidents in nuclear power plants. Transition points from thermal non-equilibrium to equilibrium are different according to the geometric effect on the critical flow. This study evaluates the uncertainty parameters of the critical flow model for analysis of DBA (Design Basis Accident) with the MARS-KS (Multi-dimensional Analysis for Reactor Safety-KINS Standard) code used as an independent regulatory assessment. The uncertainty of the critical flow model is represented by three parameters including the thermal non-equilibrium factor, discharge coefficient, and length to diameter (L/D) ratio, and their ranges are determined using large-scale Marviken test data. The uncertainty range of the thermal non-equilibrium factor is updated by the MCDA (Model Calibration through Data Assimilation) method. The updated uncertainty range is confirmed using an LBLOCA (Large Break Loss of Coolant Accident) experiment in the LOFT (Loss of Fluid Test) facility. The uncertainty ranges are also used to calculate an LBLOCA of the APR (Advanced Power Reactor) 1400 NPP (Nuclear Power Plants), focusing on the effect of the PCT (Peak Cladding Temperature). The results reveal that break flow is strongly dependent on the degree of the thermal non-equilibrium state in a ruptured pipe with a small L/D ratio. Moreover, this study provides the method to handle the thermal non-equilibrium factor, discharge coefficient, and length to diameter (L/D) ratio in the system code.

Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review

  • Castro, Fernanda Cavallari de;Cruz, Maria Helena Coelho;Leal, Claudia Lima Verde
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.8
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    • pp.1065-1074
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    • 2016
  • Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-${\beta}$) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.