• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5443-5447
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• 2014

The cholangiocarcinoma (CCA) is a relatively rare cancer worldwide but it is highly prevalent in Thailand where the liver fluke, Opisthorchis viverrini is endemic. There are reports that interleukin 6 (IL-6) may play an important role in the pathogenesis of opisthorchiasis associated CCA. Functionally, IL-6 can act on target cells through its receptor, IL-6R, and IL-6R polymorphisms may affect the functional activity of IL-6 leading to susceptibility to cholangiocarcinogenesis. Therefore, we assessed the association of the 48892 A/C (Asp358Ala) polymorphism in exon 9 of the IL-6R gene in 79 CCA cases compared to 80 healthy controls using the PCR-RFLP technique. The results showed significant differences between CCA cases and controls in overall genotype (p=0.001) and allele frequencies (p=0.0002). Chi-square for trend test revealed a significant association between genotype and CCA susceptibility (p=0.0002). The odds ratios (ORs) for genotype were 0.283 (95% CI=0.131-0.605, AC vs. AA; p=0.0003) and 0.206 (95% CI=0.196-1.245, CC vs. AA; p=0.0416), the OR for alleles was 0.347 (95% CI=0.187-0.633, allele C vs. allele A; p=0.0002) and that for the carrier C variant was 0.272 (95% CI=0.130-0.564; p=0.0001). This study demonstrated a close association between an IL-6R polymorphism, specifically higher A allele, and cholangiocarcinoma.

• Journal of Yeungnam Medical Science
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• v.24 no.2
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• pp.129-136
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• 2007

Purpose : To evaluate the chemokine expression in children with a non-productive cough. Materials and Methods : Six children with a non-productive cough who visited Yeungnam University Hospital were evaluated for the mRNA expression of interferon-${\gamma}$-inducible protein 10(IP-10), macrophage cationic protein 1 and 3 (MCP-1, 3), interleukin (IL)-8, regulated upon activation in normal T cells expressed and secreted (RANTES), eotaxin and growth-related oncogene-${\alpha}$ (Gro-${\alpha}$) using the reverse transcription polymerase chain reaction. Results : The chemokines IP-10 and MCP-3 were expressed in all samples. The chemokine RANTES was expressed in five cases, and IL-8 was expressed in three among them. However, eotaxin, Gro-${\alpha}$ and MCP-1 were not expressed at all. The expression of chemokine MCP-3, RANTES and IL-8 were suppressed after the resolution of coughing in just one available case. Conclusion : The chemokines MCP-3, RANTES and IL-8 may contribute to airway inflammation in children with a non-productive cough, whereas IP-10 is of secondary importance in this condition.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.107-128
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• 2011

Objectives : This experiment was designed to investigate the efficacy of DDTCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model. Methods : The effects of the DDTCMT hot water extract on expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II, IL-10, IL-1 receptor antagonist mRNA and production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. Expression of NO, ROS in BV2 microglial cell line treated by LPS and AChE activity in PC-12 cell treated by NGF were investigated. anti-AChE was observed through Western blot analysis. The effects of the DDTCMT hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The DDTCMT hot water extract significantly decreased the production of mIL-6, mNOS-II, mTNF-${\alpha}$, and increased the production of mIL-10, mIL-1 receptor antagonist. 2. The DDTCMT hot water extract significantly suppressed the production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by LPS. 3. The DDTCMT hot water extract significantly suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. 4. The DDTCMT hot water extract groups showed inhibition of AChE activity in NGF treated PC-12 cell line. 5. The DDTCMT hot water extract suppressed anti-AChE expression in NGF treated PC-12 cell line was observed by Western blot analysis. 6. The DDTCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine -induced impairment of memory in the experiment of Morris water maze. Conclusions : These results suggest that the DDTCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.211-219
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• 2020

Quercetin is a polyphenol compound with excellent antioxidant and anti-inflammatory activity. However, little has been reported about the efficacy of quercetin to control psoriasis. Thus, we aimed to investigate the effect of quercetin to regulate psoriatic dermatitis with HaCaT cell lines activated by TNF-α and IL-17A, which are in vitro psoriasis skin models. When quercetin was treated with TNF-α-activated HaCaT cell line, inflammatory cytokine expressions such as IL-1α, IL-1β and IL-6 were reduced by 49.1±7.14, 42.8±8.16, and 34.5±2.52%, respectively. In addition, mRNA expression levels of IL-8 and CCL20 the chemokines that attract immune cells such as Th17 cells and dendritic cells to the inflammatory reaction site, were also reduced by 38.4±5.83 and 52.9±4.59% compared to the TNF-α treatment group. The expression of proteins KRT6A and KRT16, which was nonspecifically increased in psoriatic skin was also significantly suppressed. Moreover, phosphorylation of IκBα and STAT3 proteins activated by TNF-α was also significantly inhibited. After stimulating the HaCaT with IL-17A, known as another psoriasis-inducing cytokine, it was observed that IκBα mRNA expression decreased by 55.8±5.28%, and STAT3 phosphorylation was downregulated by 36.3±6.81%. Finally, after co-activation by TNF-α/IL-17A, quercetin inhibited all of IL-1α, IL-1β, IL-6, TNF-α and CCL20 gene expression. The above results strongly suggest that quercetin is a material that has not only anti-oxidant and anti-inflammatory activities, but also has an activity in improving psoriasis.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.3
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• pp.31-46
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• 2014

Objectives Forsythiae Fructus treatment has been used for inflammatory and allergic diseases in Korean Medicine. Nevertheless, the mechanism of action and the cellular targets are not understood well. The pathogenesis of allergic diseases are associated with Th2 cytokines such as IL-13, MIP-$1{\alpha}$, IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$ and IL-6, which are secreted by the mast cells. This study was conducted to investigate the effects of Forsythiae Fructus extracts (FF) on Th2 cytokines expression and signal transduction in MC/9 mast cells. Methods In the study, MC/9 mast cells were stimulated with DNP-IgE for 24 hours and then treated separately with CsA $10{\mu}g/m{\ell}$ and varying doses of FF for one hour. MC/9 mast cells stimulated with DNP-IgE was the control group, a treatment with CsA was the positive control group and a treatment with varying doses FF was the experimental groups. The mRNA levels of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 were analyzed with Real-time PCR. The levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays(ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results 1. FF were observed to suppress the mRNA expression of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 in comparison to DNP-IgE control group. 2. FF also has inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group. 3. Western blot analysis of transduction factors involving Th2 cytokines expression has revealed a prominent decrease of the mast cell specific transduction factors including NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 but c-Fos. Conclusions In conclusion, the anti-allergenic activities of FF may be strongly related to the regulation of transcription factors NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 causing inhibition of Th2 cytokines in mast cells.

• Journal of Veterinary Clinics
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• v.38 no.6
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• pp.261-268
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• 2021

The study was conducted to evaluate the effects of carboxymethyl chitosan (CMC) on proliferation, migration, and lipopolysaccharide (LPS)-induced inflammatory response in canine bone marrow-derived mesenchymal stem cells (BMSCs). The proliferation and migration of BMSCs were examined after treatment with CMC. The effect of CMC on the mRNA expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β, was also evaluated by reverse transcription polymerase chain reaction (RT-PCR). In the proliferation assay, no significant changes were found at all CMC concentrations compared with controls. The migration assay showed that CMC dose-dependently stimulated the migration of BMSCs in normal and LPS-treated conditions. RT-PCR showed that TNF-α and IL-10 expressions were suppressed in the BMSCs after CMC treatment. However, other genes were not affected. Taken together, CMC promoted BMSC migration and inhibited TNF-α and IL-10. Therefore, CMC may be possible to regulate wound healing when mesenchymal stem cells are applied in inflammatory diseases.

• Applied Microscopy
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• v.38 no.1
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• pp.11-19
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• 2008

To examine the effect of the electrolyzed alkaline reduced water (ERW) on animal immunity, by employing Echinostoma hortense that is a parasite in the small intestine, the immune response of C57BL/6 was examined. To C57BL/6 mice, Echinostoma hortense metacercaria 15 per animal was in oculate dorsally, the worm was collected after 2 weeks, and the change of goblet cells and mast cells in the mucosa of small intestine was examined, and by using a protein chip, the change of cytokines in the serum was compared and observed. As a result, average 8.3 worms were collected from the C57BL/6 mice infected with E. hortense, and in the group fed with the ERW, average 10 worms were collected. In regard to the examination of the change of goblet cells, in the experimental group infected with E. hortense and fed with the ERW, average 4.3 worms per villus were detected, hence, it was found that the expression of goblet cells was low (p<0.001). Regarding the examination of the change of mast cells, similarly, in the group infected with E. hortense and fed with the ERW, average 11 worms per villus were detected, and it appears to be less than control group (p<0.001). Regarding the expression of cytokines in mouse serum, in comparison of the experiment group infected with E. hortense and control group, in the expression of the Th1 cytokines IL-6, IL-$1{\beta}$, IFN-${\gamma}$, TNF-${\alpha}$, and IL-2, and the Th2 cytokines IL-4, IL-5, IL-10, and IL-13, a significant difference was not detected. In our study, it was found that in the infection of E. hortense, the ERW mediates its effect on the number of goblet cells and mast cells in the intestinal mucosa, and simultaneously, the worm expulsion was delayed, and thus the conclusion that the ERW mediated its effect on the intestinal immunity of mice was obtained.

• Korean Journal of Psychosomatic Medicine
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• v.8 no.1
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• pp.46-57
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• 2000

Objectives : The purpose of the present study was to examine the effect of subacute treatment with the selective serotonin reuptake inhibitors(paroxetine and sertraline) on immobility in the forced swim test(FST) and on FST-induced changes in immune parameters of the mice. Methods : Authors applied a modified method of FST by Porsolt et al. Over 5 BALB/c mice were used for each group of experiments. To explore the changes in immune parameters by FST, authors investigated the production of anti-rat RBC antibody, concanavalin A(ConA)- or lipopolysaccharide(LPS)-stimulated splenocytes proliferation assay and cytokine gene expression. Results : Both paroxetine and sertraline decreased the duration of immobility in a dose-related manner. FST-performed mice showed a significant decrease in mitogenic responses of splenocytes and a slight increasing tendency in anti-rat RBC antibody response. All these responses were attenuated significantly by paroxetine and attenuated nearly nominal significance level by sertraline. The cytokine profiles of ConA-stimulated splenocytes from FST-performed mice showed stronger expression of IL-4 and weaker expression of IL-2 than control mice, and no changes in the expressions of IFN-$\gamma$ and lymphotoxin. IL-6 and IL-10 were not expressed in both group of mice. The pretreatment of paroxetine and sertraline attenuated the altered cytokine expressions in FST-performed mice to some extent. Some alterations of the expressions of IL-6 and IL-10 were observed in the mice which the selective serotonin reuptake inhibitors had been pretreated. Conclusion : The subacute treatment of paroxetine and sertraline attenuated the FST-induced behavioral and immune changes, and these serotonin reuptake inhibitors may exert some modulating effects on the immune system by the induction of cytokine gene expression, especially IL-6 and IL-10.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1178-1191
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• 2008

This experiment was designed to investigate the effect of the SSJHT hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the SSJHT hot water extract on expression of IL-1RA, $IL-1{\beta}$$, IL-6, IL-10, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the SSJHT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68, CD11b and AChE (3) and the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The SSJHT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$, NOS-II, COX-2 mRNA and increased IL-1RA, IL-10 in BV2 microglia cell line treated with LPS. The SSJHT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ significantly in BV2 microglial cell line treated with LPS. The SSJHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured step-through latency. The SSJHT hot water extract & ultra-fine powder suppressed the expression of $TNF-{\alpha}$$, $L-1{\beta}$ protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder significantly decreased AChE activity in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced infarction area of hippocampus. and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The results suggest that the SSJHT hot water extract & ultra-fine powder may be effective for treatment of Alzheimer's disease. Investigation into the clinical use of the SSJHT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Journal of Haehwa Medicine
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• v.24 no.2
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• pp.35-57
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• 2016

Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.