• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2151-2157
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• 2016

Scabraside D, a sulfated triterpene glycoside, was extracted from the sea cucumber Holothuria scabra. It shows anti-proliferation in many of cancer cell lines, but the function and mechanisms of action of scabraside D in human cholangiocarcinoma (HuCCA) have not previously determined. In this study, we investigated the activity of scabraside D on HuCCA cell apoptosis, lymphangiogenesis and metastasis in a nude mouse model. Scabraside D induced signs of apoptosis, such as cell shrinkage, nuclear condensation, nuclear fragmentation and DNA fragmentation on TUNEL assays, while effectively decreasing expression of BCl-2 but increasing caspase-3 gene level expression. Immunohistochemistry revealed that scabraside D significantly reduced lymphatic vessel density (LVD). Moreover, scabraside D treatment significantly decreased VEGF-C, MMP-9 and uPA gene expression, which play important roles in the lymphangiogenesis and invasion of cancer cells in metastasis processes. Quantitative real-time PCR showed that scabraside D significantly decreased iNOS and STAT-3 gene expression. This study demonstrated that scabraside D plays a role in activation of HuCCA tumor apoptosis and inhibition of lymphangiogenesis, invasion and metastasis through decreasing BCl-2, MMP-9, uPA and VEGF-C and increasing caspase-3 expression by suppression of iNOS and STAT-3 expression. Therefore, scabraside D could be a promising candidate for cholangiocarcinoma treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2439-2445
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• 2014

Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.592-597
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• 2010

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene ($stat3$) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant $Staphylococcus$ $aureus$) and $Pseudomonas$ $aeruginosa$. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count ($750/{\mu}L$) and total IgE level (5,001 U/mL). The patient's National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C>T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.533-541
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• 2016

Effect of polyphenols-rich cacao extract (CE) on lipid hydrolysis by pancreatic lipase was investigated by pH-stat digestion. Two types of substrate (oil vs. emulsion) prepared from soybean oil and CE were studied as types I and II. In the case of type I, addition of CE did not show retardation of lipid hydrolysis, showing that pancreatic lipase was not inhibited. Final digestibility rate (${\Phi}$ max, %) and initial rate (mM/s) of the 24-h aged control (52.31%, 0.03 mM/s) were similar to those of the CE-added sample (58.88%, 0.03 mM/s). However, in the case of typeII, the hydrolysis rates of the control and CE-added emulsion showed distinct differences as aging time increased to 43 days, showing lower digestion in the CE-added emulsion than the control. After 43 days, ${\Phi}$ max values of the control and CE-added emulsion were 92.13% and 77.68%, respectively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.554-561
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• 2009

Soyangin-Hyeongbangpaedok-san(SHBPDS) is a herbal formula used for the common cold or upper respiratory illness. In order to investigate the effect of SHBPDS, mice were orally administered with SHBPDS alcohol extract for 7 days followed by intravenous anti-CD3 injection. In addition, splenocytes and CD4 T cells were cultured with SHBPDS in response to anti-CD3 in vitro and cytokines and transcription factors were evaluated. In vivo treatment with SHBPDS significantly augmented the expressions of the percentage of CD4 T cells and CD 69, an indicator of early T cell activation. Serum levels of IL-4 were significantly increased but those of IFN-${\gamma}$ and IL-2 did not reach statistical significance. The expressions of IFN-${\gamma}$ and T-bet mRNA were significantly downregulated in SHBPDS treated mice while those of IL-4 and C-Maf were significantly upregulated. In vitro stimulation of splenocytes and CD4 T cells by SHBPDS resulted in a reduction in IFN-${\gamma}$ secretion and STAT4 activity. The IL-4 releases from both cells were slightly reduced, but STAT6 activity was rather increased. In conclusion, SHBPDS exerted an inhibition in the expression of IFN-${\gamma}$, T-bet and STAT4 while IL-4, C-Maf and STAT6 were increased. Further studies are required to examine its pharmacological effects using more appropriate animal experiments.

• BMB Reports
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• v.33 no.6
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.74-92
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• 2005

Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.

• KSBB Journal
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• v.15 no.2
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• pp.134-138
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• 2000

Addition of carbon and nitrogen source to an alcohol distillery wastewater was tried to increase the cell concentration of a b baker's yeast cultivated in that wastewater. Carbon was found to be primary limiting nutrient and nitrogen secondary limiting o one. Glucose addition increased the cell concentration 1.3 times higher than no addition, and both glucose and $(NH_4)_2S0_4$ a addition did 5.8 times. A fed-batch cultivation by the automatic addition of glucose and ammonium was executed. Added g glu$\infty$se was automatically controlled to low concentration by a method using DO as control parameter. Ammonium was a automatically added as NH40H used as pH $\infty$ntrol agent after initiating glucose addition. By this simple cultivation method t the cell concentration $\infty$내d be efficiently increased from 2.6g/L to 12.0g/L, and maximum specific growth rate and biomass y yield to glu$\infty$se were $0.18hr^{-1}$ and about 0.54g/g respectively. By increasing cell concentration, COD of the wastewater m media could be additionally reduced by about 22%.

• Bulletin of the Korean Chemical Society
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• v.31 no.4
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• pp.921-924
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• 2010

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.