• Journal of Life Science
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• v.19 no.12
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• pp.1690-1697
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• 2009

CD11c and costimulatory molecules such as CD80 and CD86 express mainly in dendritic cells (DCs). In this study, we investigated the biologic effects of recombinant Fms-like tyrosine kinase-3 (Flt-3) ligand on the expression of DC surface markers, including CD11c in leukemia cell lines, such as KG-1, HL-60, NB4, and THP-1 cells. The expression of the Flt-3 receptor was found in NB4 and HL-60 cells, as well as KG-1 cells, but not in THP-1 cells. When KG-1 cells were cultured in a medium containing Flt-3 ligand or granulocyte macrophage-colony stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-$\alpha$, cell proliferation was inhibited and the expression levels of CD11c, major histocompatibility complex (MHC)-I, and MHC-II were increased in the cells. Flt-3 ligand also increased the expression level of CD11c on HL-60 and NB4 cells, but not on THP-1 cells. In comparison with CD11c expression, the expression level of CD11b on KG-1 cells, but not on NB4 and HL-60 cells, was slightly increased by Flt-3 ligand. Flt-3 ligand induced phosphorylation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and p38-mitogen-activated protein kinase (p38-MAPK) in KG-1 cells, and the up-regulation of CD11c expression by Flt-3 ligand in the cells was abrogated by PD98059, an inhibitor of MEK. The results suggest that Flt-3 ligand up-regulates DC surface markers on $CD34^+$ myelomonocytic KG-1 cells, as well as promyelocytic leukemia cells, and that the differentiation of the leukemia cells into DC-like cells by Flt-3 ligand is mediated by ERK-1/2 activity.

• Journal of Acupuncture Research
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• v.18 no.4
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• pp.101-115
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• 2001

Objective : To characterize the antitumorigenic potential of Apamin, one of the major components of bee venom, its effects on cell proliferation and the mitogen-activated protein kinase (MAPK) signal transduction pathway were characterized using the human melanoma cell line SK-MEL-2. Methods & Results : Cell counting analysis for cell death demonstrated that consistent with a previous results, SK-MEL-2 cells treated with $0.5-2.0{\mu}g/ml$ of Apamin showed no recognizable cytotoxic effect whereas detectable induction of cell death was identified at concentrations over $5.0{\mu}g/ml$. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin in a dose- and time-dependent manner. To explore whether Apamin-induced growth suppression is associated with the MAPK signaling pathway, phosphorylation of Erk, a function mediator of MAPK growth-stimulating signal, was examined Western blot assay using a phospho-specific Erkl/2 antibody. A significant increase of Erkl/2 phosphorylation level was observed in Apamin-treated cells compared with untreated control cells. Qantitative RT-PCR analysis revealed that Apamin inhibit expression of MAPK downstream genes such as c-Jun, c-Fos, and cyclin D1 but not expression of MAPK pathway component genes including Ha-Ras, c-Raf-1, MEK1, and Erk. Conclusion : It is strongly suggested that the antitumorigenic activity of Apamin might result in part from its inhibitory effect on the MAPK signaling pathway in human melanoma cells SK-MEL-2.

• The Korea Journal of Herbology
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• v.39 no.1
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• pp.39-47
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• 2024

Objectives : This study evaluates how various traditional Korean herbal medicines assess MUC5AC expression for esophageal mucosal defense and analyzes the associated mechanisms involved in inflammation. Methods : Forty types of traditional Korean herbal medicines were assessed for in vitro antioxidant activities, and the real-time PCR method was employed to analyze MUC5AC expression under pH 4.5 conditions in human esophageal epithelial cells (HET-1A). Eight types of Korean herbal medicines were evaluated for in vitro antioxidant activities, and Reactive oxygen specise (ROS) expression was analyzed under bile salt (480 𝜇M) and pH 5.5 conditions in human esophageal epithelial cells (HET-1A). Simulation experiments involving bile salts and acidity were conducted for one hour to assess the efficacy of four drugs, and the activities of Mitogen-activated Protein Kinase (MEK), Nuclear Factor Kappa B (NF-𝜅B), and Cyclooxygenase-2 (COX-2) were detected through Western blot analysis. Results : Compared to the Normal group, the Control group exhibited higher ROS generation. Such increased ROS levels were significantly reduced by four extracts: Citrus Unshius Pericarpium (CUP), Cnidium officinale Rhizoma (CR), Ginseng Radix (GR), and Linderae Radix (LR). The protein expression of COX-2 decreased with the treatment of LR, CUP, and CR. Particularly, CUP and CR exhibited superior effects compared to other groups in inhibiting the phosphorylation of NF-𝜅B. Conclusion : Based on the results obtained, we have identified drugs that inhibit oxidative stress and inflammation caused by bile acid in esophageal epithelial cells. Our future plans involve comparing and analyzing the efficacy of these herbal medicines through animal experiments.

• Korean Journal of Veterinary Research
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• v.58 no.1
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• pp.1-7
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• 2018

Genus Artemisia occurs as a hardy plant and has a wide range of culinary and medicinal features. In this study, we aimed to describe the melanin inhibitory activity of one Artemisia species, i.e., Artemisia capillaris Thunb. Ethanol extracts of fermented Artemisia capillaris (Art.EtOH.FT) and non-fermented Artemisia capillaris (Art.EtOH.CT) were tested for their ability to inhibit tyrosinase activity and melanin pigmentation. Both extracts showed dose-dependent inhibition against ${\alpha}$-melanocyte stimulating hormone-stimulated melanin formation and tyrosinase activity, without cytotoxicity. At $100{\mu}g/mL$, both extracts showed greater inhibition than kojic acid, the positive control. Protein expressions of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) at the transcriptional level were determined by using real-time and semi-quantitative polymerase chain reaction. To complete the mechanistic study, presences of upstream elements of MITF, the phosphorylated-extracellular signal-regulated kinase (p-ERK), and phosphorylated-mitogen-activated protein kinase kinase (p-MEK) were confirmed by using western blot analysis. Expressions of p-TYR, p-TRP-1 and p-TRP-2, downstream factors for p-ERK and p-MITF, were translationally inhibited by both extracts. Art.EtOH.FT induced more potent effects than Art.EtOH.CT, especially signal transduction effects. In summary, Artemisia capillaris extracts appear to act as potent hypopigmentation agents.

• Applied Chemistry for Engineering
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• v.1 no.1
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• pp.91-99
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• 1990

For-${\alpha}$-APM was efficiently prepared by the reaction of For-Asp anhydride and Phe-OMe in methylethylketone, $CH_3CN$, and in water. The selective recovery of For-${\alpha}$-APM from the resulting For-${\alpha}$-APM and For-${\beta}$-APM mixture was possible via repetitive extraction at constant pH of 4.00. The oxidative deformylation was successfully performed by using several oxidants including $H_2_O2$/THF, sodium percarbonate, and $H_2_O2$/HCl/MeOH giving APM in high yields. The efficiency of the oxidative deformylation was raised in acidic condition for all the deformylation reactions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2369-2374
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• 2014

Background and Aim: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. We conduct this metaanalysis to compare the efficacy and safety of selumetinib with current therapies in patients with advanced cancer. Methods: An electronic search was conducted using PubMed/ Medicine, EMBASE and Cochrane library databases. Statistical analyses were carried out using either random-effects or fixed-effects models according to the heterogeneity of eligible studies. Results: Six eligible trials involved 601 patients were identified. Compared with current therapies, treatment schedules with selumetinib did not improve progression free survival (hazard ratio, 0.91; 95%CI 0.70-1.17, P= 0.448), but did identify better clinical benefits (odds ratio, 1.24; 95%CI 0.69-2.24, P = 0.472) and less disease progression (hazard ratio, 0.72; 95%CI 0.51-1.00, P = 0.052) though its impact was not statistically significant. Sub-group analysis resulted in significantly improved progression free survival (hazard ratio, 0.61; 95%CI 0.49-0.57, P = 0.00), clinical benefits (odds ratio, 3.04; 95%CI 1.60-5.77, P = 0.001) and reduced disease progression (hazard ratio, 0.35; 95%CI 0.18-0.67, P = 0.001) in patients administrated selumetinib. Dermatitis acneiform (risk ratio, 9.775; 95%CI 3.143-30.395, P = 0.00) and peripheral edema (risk ratio, 2.371; 95%CI 1.690-3.327, P = 0.00) are the most frequently observed adverse effects associated with selumetinib. Conclusions: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment. Dermatitis acneiform and peripheral edema are the most frequently observed adverse effects in patients with selumetinib.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.354-360
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• 2021

Background: Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods: HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results: PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) -1, -2 and -3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion: PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• Journal of Dental Rehabilitation and Applied Science
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• v.38 no.3
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• pp.150-161
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• 2022

Purpose: To determine the effects of the microgroove-fibronectin complex surface on the expression of various genes related to cellular activity in human gingival fibroblasts. Materials and Methods: Smooth titanium specimens (NE0), acid-treated titanium specimens (E0), microgroove and acid-treated titanium specimens (E60/10), fibronectin-fixed smooth titanium specimens (NE0FN), acid-treated and fibronectin-immobilized titanium specimens (E0FN), and microgroove and acid-treated titanium specimens immobilized with fibronectin (E60/10FN) were prepared. Real-time polymerase chain reaction experiments were conducted on 44 genes related to cell behavior of human gingival fibroblasts. Results: Adhesion and proliferation of human gingival fibroblast on microgroove-fibronectin complex titanium were activated through four types of signaling pathway. Integrin α5, Integrin β1, Integrin β3, Talin-2, which belong to the focal adhesion pathway, AKT1, AKT2, NF-κB, which belong to the PI3K-AKT signaling pathway, MEK2, ERK1, ERK2, which belong to the MAPK signaling pathway, and Cyclin D1, CDK4, CDK6 genes belonging to the cell cycle signaling pathway were upregulated on the microgroove-fibronectin complex titanium surface (E60/10FN). Conclusion: The microgroove-fibronectin complex titanium surface can up-regulate various genes involved in cell behavior.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.192-202
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• 2009

Background: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. Methods: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. Results: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-${\gamma}$ synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-${\kappa}B$ and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-${\gamma}$ was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. Conclusion: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages.