• IMMUNE NETWORK
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• v.16 no.1
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• pp.13-25
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• 2016

Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4⁺ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bone-marrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4⁺ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4⁺ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4⁺ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3^- regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3⁺ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

• Molecules and Cells
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• v.46 no.7
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• pp.399-413
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• 2023

cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to cis-acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.

• Molecules and Cells
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• v.37 no.10
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• pp.705-712
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• 2014

The early steps of neural development in the vertebrate embryo are regulated by sets of transcription factors that control the induction of proliferative, pluripotent neural precursors, the expansion of neural plate stem cells, and their transition to differentiating neural progenitors. These early events are critical for producing a pool of multipotent cells capable of giving rise to the multitude of neurons and glia that form the central nervous system. In this review we summarize findings from gain- and loss-of-function studies in embryos that detail the gene regulatory network responsible for these early events. We discuss whether this information is likely to be similar in mammalian embryonic and induced pluripotent stem cells that are cultured according to protocols designed to produce neurons. The similarities and differences between the embryo and stem cells may provide important guidance to stem cell protocols designed to create immature neural cells for therapeutic uses.

• Parasites, Hosts and Diseases
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• v.39 no.2
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• pp.151-160
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• 2001

Randomly selected 435 clones from Acanthamoeba healyi cDNA library were sequenced and a total of 387 expressed sequence tags (ESTs) had been generated. Based on the results of BLAST search, 130 clones (34.4%) were identified as the genes enconding surface Proteins , enzymes for DNA, energy Production or other metabolism, kinases and phosphatases, protease, proteins for signal transduction, structural and cytoskeletal proteins, cell cycle related proteins, transcription factors, transcription and translational machineries, and transporter proteins. Most of the genes (88.5%) are newly identified in the genus Acanthamoeba. Although 15 clones matched the genes of Acanthamoeba located in the public databases, twelve clones were actin gene which was the most frequently expressed gene in this study. These ESTs of Acanthamoeba would give valuable information to study the organism as a model system for biological investigations such as cytoskeleton or cell movement, signal transduction, transcriptional and translational regulations. These results would also provide clues to elucidate factors for pathogenesis in human granulomatous amoebic encephalitis or keratitis by Acanthamoeba.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Journal of Pharmacopuncture
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• v.12 no.2
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• pp.13-20
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• 2009

In this study, the effects of Ganoderma lucidum (GL) on fat metabolism were performed in 3T3-L1 adipocytes. The effects of GL on 3T3-L1 preadipocytes differentiation were also examined. Our results showed that GL decreased the TG content by ORO staining. To elucidate the mechanism of the effects of GL on lowering TG content in 3T3-L1 adipocytes, we examined whether GL modulate the expressions of transcription factors and adipokines related to control of energy expenditure process because adipokines regulate adipocyte mass and increased expenditure may consume much TG in adipocytes. As a result, the expression of C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$, genes, which induce the adipose differentiation and adipose-specific FAS, aP2, and adipsin genes, which compose fat formation were decreased. In addition, GL increased the expression of leptin, UCP2, adiponectin in 3T3-L1 adipocytes, resulting in energy homeostasis. In conclusion, GL could regulate transcript factor related to induction of adipose differentiation and control TG content by up-regulation of adipokines related to fat burn.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.40-49
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• 2023

Objectives : This study was conducted to confirm the skin anti-aging effect of Chungpyesagan-tang(CPSGT) extract. Methods : We performed MMT assay to confirm the cytotoxicity of CPSGT. After inducing matrix metalloproteinase-1(MMP-1) with tumor necrosis factor-α(TNF-α), we investigated mRNA expression and protein secretion of MMP-1 by real-time RT-PCR and ELISA. In addition, we measured the protein expression of mitogen-activated protein kinases(MAPKs) and transcription factors by western blot. Results : CPSGT was not cytotoxic at 25-800㎍/㎖. The mRNA expression and protein secretion of MMP-1 decreased when treated with CPSGT. The protein expression of p-ERK, p-JNK, p-p38 was decreased by CPSGT. In addition, the protein expression of p-c-jun and p-NF-κB, which are transcription factors, were also decreased. Conclusion : This suggests that CPSGT can inhibit MMP-1 and thus be a potential anti-aging substance.

• BMB Reports
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• v.39 no.5
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• pp.479-491
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• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

• Molecules and Cells
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• v.40 no.5
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• pp.315-321
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• 2017

The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates ($IP_4$ and $IP_5$), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity. Through its PI3-kinase activity, IPMK activates Akt/PKB and its downstream signaling pathways. IPMK also regulates several protein targets non-catalytically via protein-protein interactions. These non-catalytic targets include cytosolic signaling factors and transcription factors in the nucleus. In this review, we highlight the many known functions of mammalian IPMK in controlling cellular signaling networks and discuss future challenges related to clarifying the unknown roles IPMK plays in physiology and disease.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.1
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• pp.1-12
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• 2014

Objectives This study was performed to evaluate the effects of fermented lotus extracts on prediabetes and hyperlipidemia in high fructose diet rats. Methods Extracts of lotus leaf and lotus root were fermented using 4 different probiotics separately, including Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, and Bifidobacterium longum. Expressions of adipogenic transcription factors including Adiponectin, GLUT-4, Leptin, PPAR gamma, Resistin and Visfatin were analyzed by Real time PCR and Western blotting analysis. Results Fermented lotus extracts reduced blood glucose. Fermented lotus extracts inhibited adipogenic transcription factors by inhibiting preadipocytes differentiation. The level of gene expression of Adiponectin, GLUT-4, Leptin, PPAR gamma, Resistin and Visfatin in relation to that of GAPDH were increase or decrease significantly with the Fermented lotus formulation group. Conclusions Fermented lotus extracts showed hypoglycemic and hypolipidemic effects by inhibiting preadipocyte differentiation and controlling insulin sensitivity in high fructose diet rats.