• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3043-3050
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• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.263-291
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• 2009

Objectives The purpose of this study is to investigate the effect of YHJST on atopic dermatitis in an experiment using an NC/Nga mice induced by DNCB, which has histological and clinical similarities to the condition in humans. Methods To investigate the effect of YHJST on atopic dermatitis(AD), we evaluated atopic dermatitis-like skin lesions by clinical skin index and analyzed immunological parameters in peripheral blood mononuclear cells(PBMCs) and performed skin histology in ears and dorsal skin of NC/Nga ato-mouse. Results YHJST medicines decreased Serum level of IgE, IL-6, TNF-$\alpha$. Also total number of $CD69^+$, $CD3^+$ in PBMCs, absolute cell number of $CCR3^+CD3^+$, $CD11b^+Gr-1^+$ in Dorsal skin tissue, Serum IgG1, IgM, IgG2a and IgG2b decreased significantly. Furthermore YHJST is extremely effective to histological symptoms; dermal and epidermal thickening, hyperkeratosis and inflammatory cell infiltration and suppressed histologic infiltration of $CD4^+$ & $CCR3^+$ in ear and dorsal skin lesions significantly. YHJST decreased gene-expression of IL-6, TNF-$\alpha$, CCR3, Eotaxin mRNA than that of control group. Conclusions YHJST on atopic dermatitis to atopic dermatitis NC/Nga mouse induced DNCB was incredibly effective.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.443-451
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• 2009

Soyangin-Hyeongbangpaedok-san(SHBPDS) is used for treating upper respiratory infections, In an effort to investigate the anti-inflammatory effects of SHBPDS, we measured production of several cytokines and immunoglobulin in various immune cells. SHBPDS decreased the secretion of TNF-${\alpha}$, but not that of IL-6 in PMA/A23187 stimulated HMC-1 cells. As for mouse B cells, it induced proliferation and caused differential effects in expressions of surface IgE as determined by flow cytometry and secretions of IgE, IgG1, ILA and INF-${\gamma}$as measured by ELISA but showed little change in CD23 or CD69 expression. SHBPDS increased proliferation in anti-CD3/anti-CD28 stimulated CD4 Th cells. Under the Th1/Th2 polarization conditions, SHBPDS at 200 ${\mu}g/m{\ell}$ suppressed the secretion of INF-${\gamma}$ and IL-4. Based on the above results, we conclude that SHBPDS has antiinflammatory activities in mast cells and different immunomodulatroy effects in B cells and Th cells.

• Molecules and Cells
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• v.25 no.2
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• pp.216-223
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• 2008

It has been reported that bone marrow (BM)-side population (SP) cells, with hematopoietic stem cell activity, can transdifferentiate into cardiomyocytes and contribute to myocardial repair. However, this has been questioned by recent studies showing that hematopoietic stem cells (HSCs) adopt a hematopoietic cell lineage in the ischemic myocardium. The present study was designed to investigate whether BM-SP cells can in fact transdifferentiate into functional cardiomyocytes. Phenotypically, BM-SP cells were $19.59%{\pm}9.00\;CD14^+$, $8.22%{\pm}2.72\;CD34^+$, $92.93%{\pm}2.68\;CD44^+$, $91.86%{\pm}4.07\;CD45^+$, $28.48%{\pm}2.24\;c-kit^+$, $71.09%{\pm}3.67\;Sca-1^+$. Expression of endothelial cell markers (CD31, Flk-1, Tie-2 and VEGF-A) was higher in BM-SP cells than whole BM cells. After five days of co-culture with neonatal cardiomyocytes, $7.2%{\pm}1.2$ of the BM-SP cells expressed sarcomeric ${\alpha}$-actinin as measured by flow cytometry. Moreover, BM-SP cells co-cultured on neonatal cardiomyocytes fixed to inhibit cell fusion also expressed sarcomeric ${\alpha}$-actinin. The co-cultured BM-SP cells showed neonatal cardiomyocyte-like action potentials of relatively long duration and shallow resting membrane potential. They also generated calcium transients with amplitude and duration similar to those of neonatal cardiomyocytes. These results show that BM-SP cells are capable of functional cardiomyogenic differentiation when co-cultured with neonatal cardiomyocytes.

• Molecules and Cells
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• v.27 no.2
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• pp.251-255
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• 2009

Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopolysaccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethylenetriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 ($K_d$, $9.52{\times}10^{-8}M$). It dose dependently inhibited LPS-mediated activation of human myeloid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on $NF-{\kappa}B$ activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results suggest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3967-3971
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• 2012

Aims: To explore the relationship between various molecular makers and liver metastasis of colorectal cancer (CRC). Method: Using immunohistochemistry, protein expression of CEA, nm23, c-met, MMP2, COX-2, VEGF, EGFR, and CD44 was assessed in 80 CRC cases. The Chi-square test and logistic regression were performed to analyze the relationship between these indicators and CRC liver metastasis. Results: There were significant differences in expression of CEA, MMP2, CD44, VEGF and EGFR between the liver metastasis and non metastasis groups (P < 0.05); no significant differences were noted for nm23, c-met, and COX-2 expression. Logistic regression analysis showed that only CEA, VEGF, and EGFR entered into the regression equation, and had significant correlations with CRC liver metastasis (${\alpha}$ inclusion= 0.10, ${\alpha}$ elimination = 0.15, R2 = 0.718). Conclusions: Combination detection of CEA, VEGF, and EGFR may be an effective means to predict CRC liver metastasis. Nm23, c-met, MMP2, COX-2, and CD44, in contrast, are not suitable as prognostic markers.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.936-941
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• 2005

In this trial we assessed the effect of soluble alginates on murine cells. Mouse peritoneal monocytes were stimulated in vitro with a solution of alginate. The production of $TNF-\alpha$ and nitric oxide (NO), the expression of surface molecules CD80 and CD86, and the ability of monocytes to phagocyte bacteria were assessed, in order to evaluate the effect of alginate on cell functionality. We showed that mouse peritoneal monocytes stimulated with alginate produce NO and $TNF-\alpha$. In addition, alginate is able also to increase their phagocytic activity and to a lesser extent also to increase the expression of CD80. Even with different degrees, it implies that alginates per se act directly on immune response, being able to effectively stimulate proinflammatory activity. These findings corroborate the idea that alginates can represent interesting adjuvants to use to increase the efficacy of antigenic stimulation.

• Journal of Oriental Neuropsychiatry
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• v.19 no.2
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• pp.41-64
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• 2008

Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer's disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with 13A were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group 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 stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}A$. 3. The Hominis Placenta Herbal Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer's disease is suggested for future research.

• Gut and Liver
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• v.12 no.6
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.181-189
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• 2007

To examine the effects of HHCP on atopic dermatitis and its various immunopathologic parameters was induced by DNCB in NC/Nga mice and the animals were orally administrated with HHCP. We summarized the results obtained from serum levels of IgE and the numbers of various immune cells as follow. HHCP has no cytotoxic effects at the range of concentration (1-400 ${\mu}g$/ml) on fibroblast isolated from lung of BALB/c mice. HHCP significantly lowered the serum levels of IgE compared with control at 16 and 20 week. HHCP significantly reduced the number of CD19$^+$ cell in spleen and DLN, as well as the number of B220$^+$ /IgE$^+$ cell in DLN compared with control. HHCP significantly reduced the number of ${\alpha}$${\beta}$ TCR$^+$ in spleen and DLN, the number of CD8$^+$ in spleen compared with control, and also significantly reduced the number of CD3$^+$, CCR3, CD3$^+$/CD69$^+$, CD3/ CCR3, CD4$^+$, CD3$^+$/ CD4$^+$/CD45$^+$ cell in DLN. HHCP increased the number of NK$^+$ cells in spleen compared with control, in contrast significantly decreased the number of CD11c$^+$/ Classll$^+$ cell and CD11b$^+$/Gr-1$^+$ cell in DLN. Taken together, these results suggested that HHCP has suppressive effects on atopic dermatitis through the inhibition of IgE production and modulation of immune cell population in NC/Nga mice.