• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.301-308
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• 2017

27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.881-886
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• 2001

The purpose of this study was to Investigate the effects of green tea catechin on changes of mineral contents in chronic cadmium-poisoned rats. Sprague-Dawley male rats weighing 100 $\pm$ 10g were randomly assigned one of normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group), 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raised for 20 weeks. Cadmium was supplied in drinking water which contained 50ppm Cd$^{2+}$. Effects of catechin were analyzed on changes of mineral contents in chronic cadmium poisoned rats by determining the calcium accumulation in bones, blood, urine and faces and phosphorus In blood and urine. Cd-poisoning inducted the decrease of red blood cell(RBC), white blood cell(WBC), contents of blood hemoglobin and hematocrit, but the levels of those indices were increased by catechin supplementation. The contents of tibia and femur in Cd-0C group was significantly lower than in normal group, but those of catechin supplemetation group was similar to normal group. The calcium contents of urine and faces were higher in Cd-poisoned groups than in normal group, but they was lowered by catechin supplementation. The phosphorus contents of blood and urine in Cd-0C group was significantly lower than in normal group, but that of catechin supplementation group was similar to normal group. Catechin supplementation improved the calcium metabolism in chronic cadmium poisoned rats by increasing the contents of minerals such as calcium and phosphorus in blood and femur and by lowering the urinary and fecal calcium.m.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.221-227
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• 2014

Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.277-283
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• 2012

Vitamin C is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostasis, but the mechanism related to immune-potentiation is poorly understood. Since dendritic cells (DCs) are known as a potent antigen presenting cell (APC) that could enhance the antigen specific immune responses, we investigate the effects of vitamin C on activation of DCs and its related mechanism by using dendritic cell lines, DC-1. First, we found that there was no damage on DC-1 by 2.5 mM of vitamin C. In the presence of vitamin C, the expression of CD80, CD86, and MHC molecules was increased, but it was decreased by the pre-treatment of SB203580, p38 MAPK-specific inhibitor. We confirmed the phosphorylation of p38 MAPK was increased by the treatment of vitamin C. Taken together, these results suggest that vitamin C could enhance the activity of dendritic cells via the up-regulation of the expression of CD80, CD86, and MHC molecules and the activation of p38 MAPK is related to this process.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• Journal of Environmental Health Sciences
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• v.38 no.4
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• pp.323-331
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• 2012

Objectives: The objective of this study was to investigate the possible effects of environmental cadmium (Cd) exposure on of bone mineral density (BMD) levels. Methods: A total of 171 residents around abandoned mines in Chungcheongnam-do were surveyed in 2008-2011. Urinary Cd and BMD were analyzed by atomic absorption spectrometry and Dual-Energy X-ray absorptionmetry, respectively. Osteoporosis and osteopenia were defined by T-scores set by the WHO; Tscore ${\geq}$ -1.0, normal; -1.0 > T-score > -2.5, osteopenia; and T-score ${\leq}$ -2.5, osteoporosis. Logistic and multiple linear regressions were applied to estimate the association between U-Cd levels and BMD. Results: The U-Cd geometric mean of 171 Koreans was 2.79 ${\mu}g/g{\cdot}cr$. The U-Cd concentration was significantly higher among women (2.98 ${\mu}g/g{\cdot}cr$) than men (2.39 ${\mu}g/g{\cdot}cr$). With the multiple regression model, the BMD was influenced by U-Cd, BMI, and monthly income. With the logistic regression model, osteoporosis was associated with U-Cd levels (OR = 3.239, 95% CI = 1.770-5.927). Conclusions: We conclude that exposure to cadmium is associated with an increased risk of osteoporosis.

• Herbal Formula Science
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• v.21 no.1
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• pp.161-176
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• 2013

Objectives : To clarify the anti-arthritic activity of Ostericum koreanum Maxim. (OS) plus Aralia continentalis Kitagawa (AC) in vivo. Methods : All mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with OS plus AC once a day for 7 weeks. Oral administration of OS plus AC (200 or 50 mg/kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/kg), a positive control. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of OS plus AC significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with OS plus AC. In conclusion, our results demonstrates that OS plus AC significantly suppressed the progression of CIA and that this action was characterized by the decreased production of IL-6, IFN-${\gamma}$ and collagen II specific antibody in serum, CD3+CD69+ T cells, MHC class II+/CD11c+ (in DLN), CD11b+Gr-1+ cells (in PBMC), CD11b +Gr-1+ cells, B220+/CD23+ (in paw joint). Conclusions : The the levels of IFN-${\gamma}$ in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. In the serum of OS and AC-treated mice, the levels of IgM RA factor were decreased.

• Molecules and Cells
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• v.28 no.6
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• pp.553-558
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• 2009

In the periphery, a galectin-1 receptor, CD7, plays crucial roles in galectin-1-mediated apoptosis of activated T-cells as well as progression of T-lymphoma. Previously, we demonstrated that $NF-{\kappa}B$ downregulated CD7 gene expression through the p38 MAPK pathway in developing immature thymocytes. However, its regulatory pathway is not well understood in functional mature T-cells. Here, we show that CD7 expression was downregulated by Twist2 in Jurkat cells, a human acute T-cell lymphoma cell line, and in EL4 cells, a mature murine T-cell lymphoma cell line. Furthermore, ectopic expression of Twist2 in Jurkat cells reduced galectin-1-induced apoptosis. While full-length Twist2 decreased CD7 promoter activity, a C-terminal deletion form of Twist2 reversed its inhibition, suggesting an important role of the C-terminus in CD7 regulation. In addition, CD7 expression was enhanced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate, which indicates that Twist2 might be one of candidate factors involved in histone deacetylation. Based on these results, we conclude that upregulation of Twist2 increases the resistance to galectin-1-mediated-apoptosis, which may have significant implications for the progression of some T-cells into tumors such as Sezary cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1389-1393
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• 2012

Objective: To discuss the significance of DOG1, CD117 and PDGFRA in the diagnosis of gastrointestinal stromal tumors (GISTs), and analyze their correlations with clinicopathological features and risk ranking. Method: DOG1, CD117 and PDGFRA were detected with IHC Envision ldpe-g-nvp in 63 GISTs and 43 cases of non-GISTs, and analyzed for relations with clinicopathological factors (gender, age, location, tumor size, mitotic phase, histology) and risk degree. Results: The positive expression rate of DOG1, CD117 and PDGFRA in GISTs was 84.1% (53/63), 90.5% (57/63), 53.2% (33/63), respectively. Among the 6 CD117 negative cases, all were DOG1 positive and 5 were PDGFRA positive. Rates in patients with non-GISTs was 11.6%, 16.3%, 6.98%, respectively. Expression of DOG1 and PDGFRA demonstrated no significant variation with gender, age, position, tumor size, mitotic phase, histology, and risk rank. However, CD117 was related with position and histology (P=0.008 and P=0.045), those in the mesentery having a higher positive rate than those derived from stomach, small intestine, colon and rectum (50.0% vs 94.7%, P=0.008). Furthermore CD117 was also highly expressed in spindle and epithele types. Conclusions: DOG1 had a good sensitivity and specificity as a kind of newly discovered marker, especially for KIT negative GISTs. However, DOG1, CD117 and PDGFRA cannot be used for assessing the rish of patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3751-3755
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• 2012

Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.