• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.362.2-362
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• 1998

No Abstract, See Full Text

• 대한생식의학회:학술대회논문집
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• 1997.11a
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• pp.66-67
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• 1997

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.265-271
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• 2016

Recently, liver damage contributes to big percentage of the morbidity and mortality rates worldwide. Excessive intake of alcohol is one of the major causes of liver injury. When liver injury is repeated and becomes chronic, it leads to development of fibrosis and cirrhosis. In the liver, TGF-${\beta}$ is a profibrogenic cytokine, which participates in various critical events cause liver fibrosis. Seahorse (Hippocampus abdominalis) is a common traditional Chinese medicine and has been widely used for centuries. Seahorse has been known to have a variety of bioactivities, such as anti-oxidant, anti-fatigue, and anti-tumor. Peptide is one of the main compounds of seahorse. In this study, we isolated enzymatic hydrolysate from seahorse H. abdominalis by alcalase hydrolysis and investigated the effect of the hydrolysate on liver injury. In the present in vitro studies, the hydrolysate increases cell viability of Chang cells and protects Huh7 cells from ethanol toxicity. In addition, the hydrolysate inhibits TGF-${\beta}$-induced responses. In vivo studies show that the pretreatment of hydrolysate reduces alcohol-induced increases of serum Glutamic oxaloacetic acid transaminase and Glutamic pyruvate transaminase activities and increases liver weight and body weight. These results suggest that seahorse may have a hepatoprotective effect.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6813-6820
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• 2013

The present study was conducted to investigate the prognostic significance of co-expression patterna of HER-2, IL-6, TNF-a and TGF-${\beta}1$ in breast cancer, by correlating the number of markers with positive expression with clinicopathological characteristics indicative of tumor progression and overall survival. One hundred thirty consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of the above markers were measured by ELISA. Median split was used to subdivide patients with marker positive or negative expression. The presence of ${\geq}3$ positive markers was independently associated with extended lymph node (>3) involvement (aOR, 11.94, p=0.001) and lymphovascular invasion (aOR, 12.04, p=0.018), increasing the prognostic significance of each marker considered separately. Additional prognostic information regarding survival was also provided; as the number of positive markers increased, a gradually reduction of survival time was observed. In addition, patients with 4 positive markers had significantly shorter survival (25 vs 39 months, p=0.006) and a more than 4 fold increased risk of death (aHR, 4.35, p=0.003) compared to patients with 3 positive markers. Our findings suggest that the coexpression pattern of these four markers could be used clinically as a useful marker for tumor extension and outcome of breast cancer.

• BMB Reports
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• v.39 no.6
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.128-139
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• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.51-66
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• 2004

Objectives : To evaluate experimentally the clinical effect of Bojeongjeongcheon-tang, we observed the cytokines ($IL-1{\beta}$/TEX>, IL-4, IL-5, IL-6, IL-10, TNF-{\alpha},{\;}TGF-{\beta},{\;}IFN-{\gamma}$) and what effect they have on IgE in B cells of a rat. Methods : First of all, we extracted the spleens of healthy Balb/c mice and separated B cells from them. These B cells were cultured with anti-CD40 mAb (500 ng/ml), rmIL-4 (500 U/ml), Bojeongjeongcheon-tang (100 ug/ml, 10 ug/ml, 1 ug/ml). We used rmiL-10 (50 ng/ml) as a control group. Furthermore, we analyzed the expression of IgE, CD23, CD69 and the coherence of HRF in B cells using a flow cytometer. We also analyzed the cytokine gene expression in B cells by reverse transcriptase-PCR. We also measured B cells proliferation using the Liquid Scintillation Counter. Results : In this study, the Bojeongjeongcheon-tang treated group showed a tendency to decrease depending on the density compared with the control group in the expression of IgE+, CD23+, CD69, HRF. All of the Bojeongjeongcheon-tang treated group showed inhibitory effects with $IL-1{\beta}$, IL-4, IL-5 and proliferating effects with IL-6, IL-10, and $IFN-{\gamma}$ on cytokines transcript expression depending on the density. Meanwhile, $TNF-{\alpha}$ increased in all density. In IgE production, there was inhibitory effect on Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml) of significance (p < 0.01, p < 0.05). Also in B cell proliferation, the result revealed an inhibitory effect of Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml), of significance (p < 0.001, p < 0.01). Conclusions : This study shows that Bojeongjeongcheon-tang has an inhibitory effect on the production and activity of B cells. Also it inhibited CD23, IL-4 activity and IgE production and activation. It is obvious that Bojeongjeongcheon-tang treats asthma by inhibiting the production of histamine and HRF, IL-5 and proliferating IL-10. Also Bojeongjeongcheon-tang has some preventive effects on bronchial change by inhibiting $TGF-{\beta}$, which stimulates the bronchial transformation.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.434-445
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• 2023

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

• BMB Reports
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• v.51 no.11
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• pp.545-546
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• 2018

With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7289-7294
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• 2013

We here document discovery of a new and simple model of tumor seeding involving the mouse peritoneum. Irradiated tumor cells administered by i.p. injection provided effective vaccination against peritoneal carcinomatosis and distal metastasis with colorectal carcinomas. In flow cytometric analysis, CD4+ and CD8+ T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which are easy to obtain in the peritoneal cavity, were revealed to have significant differences between immunized and non-immunized mice and these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluid harvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase in level of TGF-${\beta}1$ and IL-10 in serum but a decrease of TGF-${\beta}1$ in peritoneum was found. Taken together, these findings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis of carcinomas through induction of an autoimmune response in the peritoneum.