• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.4
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• pp.342-349
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• 2023

Backgrounds/Aims: Liver organoids have emerged as a powerful tool for studying liver biology and disease and for developing new therapies and regenerative medicine approaches. For organoid culture, Matrigel, a type of extracellular matrix, is the most commonly used material. However, Matrigel cannot be used for clinical applications due to the presence of unknown proteins that can cause immune rejection, batch-to-batch variability, and angiogenesis. Methods: To obtain human primary hepatocytes (hPHs), we performed 2 steps collagenase liver perfusion protocol. We treated three small molecules cocktails (A83-01, CHIR99021, and HGF) for reprogramming the hPHs into human chemically derived hepatic progenitors (hCdHs) and used hCdHs to generate liver organoids. Results: In this study, we report the generation of liver organoids in a collagen scaffold using hCdHs. In comparison with adult liver (or primary hepatocyte)-derived organoids with collagen scaffold (hALO_C), hCdH-derived organoids in a collagen scaffold (hCdHO_C) showed a 10-fold increase in organoid generation efficiency with higher expression of liver- or liver progenitor-specific markers. Moreover, we demonstrated that hCdHO_C could differentiate into hepatic organoids (hCdHO_C_DM), indicating the potential of these organoids as a platform for drug screening. Conclusions: Overall, our study highlights the potential of hCdHO_C as a tool for liver research and presents a new approach for generating liver organoids using hCdHs with a collagen scaffold.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.231-237
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• 2010

Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

• BMB Reports
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• v.45 no.3
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• pp.159-164
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• 2012

CD99 is known to be involved in the regulation of cell-cell adhesion. However, it remains unclear whether CD99 controls cell-extracellular matrix adhesion. In this study, the effects of CD99 activation on cell-extracellular matrix adhesion were investigated. It was found that engagement of CD99 with the stimulating antibody YG32 downregulated the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV in a dose-dependent manner. The CD99 effect on cell-ECM adhesion was inhibited by overexpression of the dominant negative form of CD99 or CD99 siRNA transfection. Treatment of cells with $Mn^{2+}$ or by ${\beta}_1$ integrin-stimulating antibody restored the inhibitory effect of CD99 on cell-ECM adhesion. Cross-linking CD99 inactivated ${\beta}_1$ integrin through conformational change. CD99 activation caused dephosphorylation at Tyr-397 in FAK, which was restored by the ${\beta}_1$ stimulating antibody. Taken together, these results provide the first evidence that CD99 inhibits cell-extracellular matrix adhesion by suppressing ${\beta}_1$ integrin affinity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5409-5413
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• 2012

At present, multiple myeloma (MM) remains an incurable disease and cologenic cells may be responsible for disease relapse. It has been proposed that CD20+/CD138- NCI-H929 cells could be hallmarks of MM clonogenic cells. Here, the immunology phenotype of NCI-H929 cells is described. Only a small population of CD20+/CD138- cells (<1%) was found in the NCI-H929 cell line, but CD20+/CD138- cells were not detected. We found that CD20+/CD138+ cells were able to exhibit cologenic capacity by colony formation assay and continuous passage culture. Proteins were analyzed by 1D-SDS-PAGE and TMT based quantitative differential liquid chromatography tandem mass spectrometry (LC-MS/MS). 1,082 non-redundant proteins were identified, 658 of which were differentially expressed with at least a 1.5-fold difference. 205 proteins in CD20+ cells were expressed at higher levels and 453 proteins were at lower levels compared with CD20- cells. Most proteins had catalytic and binding activity and mainly participated in metabolic processes, cell communication and molecular transport. These results proved that there are different biological features and protein expression profile between CD20+ and CD20- cells in the NCI-H929 cell line.

• Bulletin of the Korean Chemical Society
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• v.25 no.2
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• pp.216-220
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• 2004

${\beta}$-CD and CM- ${\beta}$-CD as chiral NMR shift agents were used to resolve the enantiomers of noradrenaline (NA). The stoichiometry of each complex formed between the CDs and the enantiomers of NA was found to be 1 : 1 through the continuous variation plots. The binding constants (K) of the complexes were determined from $^1H$ NMR titration curves. This result indicated that both ${\beta}$-CD and CM- ${\beta}$-CD formed the complexes with the S(+)-NA more preferentially than its R(-)-enantiomer. The K values for the complexes with ${\beta}$-CD ($K_{S(+)}$ = 537 $M^{-1}$ and $K_{R(-)}$ = 516 $M^{-1}$ was larger than those with CM- ${\beta}$-CD ($K_{S(+)}$ = 435 $M^{-1}$ and $K_{R(-)}$ = 313 $M^{-1}$), however, enantioselectivity (${\alpha}$) of S(+)- and R(-)-NA to CM- ${\beta}$-CD ( ${\alpha}$ = 1.38) was larger than that to ${\beta}$-CD ( ${\alpha}$ = 1.04), indicating that CM- ${\beta}$-CD was the better chiral NMR solvating agents for the recognition of the enantiomers of NA. Two dimensional rotating frame nuclear Overhauser enhancement spectroscopy (ROESY) experiments were also performed to explain the binding properties in terms of spatial fitting of the NA molecule into the macrocyclic cavities.

• Korean Journal of Acupuncture
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• v.24 no.4
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• pp.111-129
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Coicis Semen Herbal-acupuncture solution (CS-HAS) at the Joksamni (ST36) on the collagen-induced arthritis in the DBA/1J mouse. The author performed several experiments to analyze the effects of CS-HAS on arthritis; change of the weight; the spleen size and adhesion rate; serum cytokine levels; serum antibody levels; changes of immunocyte counts; the histological changes of joint. Results : In the Coicis Semen Herbal-acupuncture (CS-HA), arthritis index, the incidence of arthritis, and the degree of joint edema were decreased. In CS-HA, there was no weight loss. The size of the spleen, adhesion rate, and the edema and transformation of joint were lowered. In CS-HA, the levels of IL-1${\beta}$, IL-6, TNF-${\alpha}$, IFN-${\gamma}$, IgG, IgM, and anti-collagen II in serum and the levels of IFN-${\gamma}$, IL-4, IL-10 in spleen were significantly decreased. In CS-HA, the expression ratios of $CD45^+$ to $CD3e^+$ and $CD8^+$ to $CD4^+$ were decreased. Also, the overall $CD4^+/CD8^+$ cell ratio was lowered in spleen. Ratios of the $CD4^+/CD25^+$, $CD45^+/CD69^+$ cells were decreased in lymph nodes. In addition, ratios of the $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ cells were also decreased in synovium. In the histological study, the cartilage destruction and synovial cell proliferation, and collagen fiber destruction were decreased with CS-HA treated group. Conclusions : From the results mentioned above, it is suggested that CS-HA at the ST36 has several significant effects on the collagen-induced arthritis.

• Environmental Engineering Research
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• v.22 no.3
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• pp.281-287
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• 2017

The joint effect of different concentrations (0.05-0.375 mmol/L) of $Cd^{2+}$ and various concentrations (50-400 mg/L) of [$C_3mim$][OAc] on the growth and physiology of wheat seedlings were investigated. The toxicity of $Cd^{2+}$ could be significantly reduced by lower concentrations (50-200 mg/L) of [$C_3mim$][OAc]. With higher concentration (${\geq}300mg/L$) of [$C_3mim$][OAc], the reduction became less, and compared to $Cd^{2+}$ stress only, the toxicity of 400 mg/L [$C_3mim$][OAc] increased. As for different $Cd^{2+}$ concentrations, the optimal reduction depends on the balance between the exact concentration of $Cd^{2+}$ and [$C_3mim$][OAc]: With low $Cd^{2+}$ concentration (0.05-0.250 mmol/L) requiring 50 mg/L [$C_3mim$][OAc], it could reach a dynamic equilibrium, while high $Cd^{2+}$ concentration (0.375 mmol/L) requiring 100 mg/L [$C_3mim$][OAc]. The growth and physiological indexes of wheat seedlings show a decrease in toxicity compared to the Cd alone treatment, when the dynamic equilibrium is reached. The concentration of $Cd^{2+}$ in leaf tissues showed that low concentration (50-200 mg/L) of [$C_3mim$][OAc] can reduce the toxicity of $Cd^{2+}$ (0.05-0.375 mmol/L) by decreasing the level of $Cd^{2+}$ concentration in the tissues, whereas the higher concentration (${\geq}300mg/L$) of [$C_3mim$][OAc] can increase the concentration of $Cd^{2+}$.

• Clean Technology
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• v.19 no.3
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• pp.212-218
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• 2013

The microparticles of 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) were prepared using aerosol solvent extraction system (ASES) by employing supercritical carbon dioxide as an antisolvent, The effects of various process parameters such as temperature, pressure, solution concentration and solution flow rate on the formation of HP-${\beta}$-CD microparticles were investigated. The HP-${\beta}$-CD microparticles prepared by the ASES process were observed to consist of agglomerates of nano-sized (50-200 nm) particles. When an aqueous solution of ethanol was used as a solvent for HP-${\beta}$-CD, the HP-${\beta}$-CD particles were found to be spherical in shape and to become larger as the water content increased. It was confirmed that the micronization of HP-${\beta}$-CD using the ASES process could enhance the inclusion efficiency of ibuprofen/HP-${\beta}$-CD complexes significantly.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2219-2224
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• 2012

Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of $CD4^+$, $CD19^+$, $CD44^+$, $CD25^+$, NK cells, and an increased $CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating $CD19^+$ lymphocytes compared to those with low $CD19^+$ lymphocytes (P=0.037), with $CD19^+$ showing an important cutoff of $7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival.