• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.243-254
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• 1994

Inflammatory diseases, allergic and asthmatic disorders are caused by the mediator release from the activation of the phospholipase C (PLC), phospholipase D (PLD), methyltransferase or adenylate cyclase etc. during IgG or IgE cross-linking of high affinity receptors on mast cells or basophil surface. One important enzyme activated after IgG or IgE receptor cross-linking is PLD, the enzyme which converts phosphatidylcholine (PC) to phosphatidic acid (PA). Under the hypothesis that these may be some differences in mediator release according to the difference in PLD activity, we attempted to confirm the ginseng saponin effects on the PLD activity. We examined the PLD activity during the passively sensitized mast cell activation in the presence of single component of ginsenosides $(Rc,\;Rg_1,\;Rg_2,\;Rg_3)$. We also measured the amount of mediators (histamine and leukotrienes) released by stimulating with ovalbumin (OA) or calcium ionophore (CaI), Guinea Pig lung mast cells were purified using enzyme digestion, count current elutriation, and discontinuous Percoll density gradient. In purified mast cells prelabeled with $[^3H]$ arachidonic acid or $[^3H]$ palmitic acid, PLD activity was assessed more directly by the production of labeled PEt by PLD-mediated transphosphatidylation in the presence of ethanol. Histanine release was determined by Spectrophotofluorometry, and leukotrienes by radioimmunoassay. The PLD activity during the passively sensitized mast cell activation is increased up to $3{\sim}5times$. The PLD activity during the passively sensitized mast cell activation in the presence of all ginsenosides is decreased up to $4{\sim}11$ times. $Rg_l\;and\;Rg_2$ ginsenoside pretreatment decreased histamine and leukotrienes by 50% in the OA-induced or by 40% in the Cal-induced mast cell after passively sensitization. Rc pretreatment poorly decreased histamine but leukotrienes decreased by 70% in the OA-induced or by 35% in the Cal-induced mast cell. $Rg_3$ ginsenoside pretreatment increased histamine release without challenging OA or Cal but leukotrienes decreased. These observations indicate that single unit of ginsenosldes may be an important contributor to inhibit the release of histamine and leukotrienes in the guinea pig lung mast cells, that inhibits the PLD-mediated formation of DAG evoked by mast cell activation.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.11-16
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• 2012

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; $25{\mu}g/ml$) and methotrexate (MTX; $50{\mu}g/ml$), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Toxicological Research
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• v.28 no.1
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• pp.25-31
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• 2012

The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at $1.93{\times}10^7$ particles/$cm^3$, $1.09{\times}10^{10}\;nm^2/cm^3$, $2.72{\times}10^{11}\;nm^3/cm^3$, and 2854.62 ${\mu}g/m^3$, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• Applied Chemistry for Engineering
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• v.30 no.4
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• pp.429-434
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• 2019

A lateral flow immunoassay platform utilizing antibody functionalized water soluble CdSe/ZnS semiconductor quantum dots (QDs) was developed for the analysis of human serum amyloid A-1 (hSAA1) in a buffer solution. hSAA1 was chosen as a target protein because it is regarded as a potential biomarker associated with early diagnosis and prognosis in patients of lung cancer. The immunoassay strip on a nitrocellulose membrane was fabricated by spraying two lines composed of a test line with a monoclonal antibody against hSAA1 (10G1) (anti hSAA1) and a control line of anti-chicken IgY. While the CdSe/ZnS QDs synthesized in an organic phase were transferred to a water phase by ligand exchange using carboxylic acid modified alkane thiol. The QDs was then conjugated to monoclonal antibody against hSAA1 (14F8) [anti hSAA1 (14F8)] and used as a fluorescent detection probe. The sequential lateral flow of hSAA1 in different concentration and QDs-anti hSAA1 (14F8) complex allowed to form the surface sandwich complex of anti hSAA1 (10G1)/hSAA1/QD-anti hSAA1 (14F8), which was then analyzed using fluorescence microscope. A 100 nM concentration of hSAA1 protein can be detected by naked eyes under an optimized lateral flow buffer condition with a sensing time of 5 mins.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.156-166
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• 2022

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (K_D value of 1.16 × 10^-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

• Journal of Radiation Protection and Research
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• v.48 no.4
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• pp.197-203
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• 2023

Background: The thermoluminescent dosimeter (TLD) and Monte Carlo (MC) dosimetry are carried out to determine the occupational dose for personnel in the handling of ¹²⁵I seed sources. Materials and Methods: TLDs were placed in different layers of the Alderson-Rando phantom in the thyroid, lung and also eyes and skin surface. An ¹²⁵I seed source was prepared and its activity was measured using a dose calibrator and was placed at two distances of 20 and 50 cm from the Alderson-Rando phantom. In addition, the Monte Carlo N-Particle Extended (MCNPX 2.6.0) code and a computational phantom with a lattice-based geometry were used for organ dose calculations. Results and Discussion: The comparison of TLD and MC results in the thyroid and lung is consistent. Although the relative difference of MC dosimetry to TLD for the eyes was between 4% and 13% and for the skin between 19% and 23%, because of the existence of a higher uncertainty regarding TLD positioning in the eye and skin, these inaccuracies can also be acceptable. The isodose distribution was calculated in the cross-section of the head phantom when the ¹²⁵I seed was at two distances of 20 and 50 cm and it showed that the greatest dose reduction was observed for the eyes, skin, thyroid, and lungs, respectively. The results of MC dosimetry indicated that for near the head positions (distance of 20 cm) the absorbed dose rates for the eye lens, eye and skin were 78.1±2.3, 59.0±1.8, and 10.7±0.7 µGy/mCi/hr, respectively. Furthermore, we found that a 30 cm displacement for the ¹²⁵I seed reduced the eye and skin doses by at least 3- and 2-fold, respectively. Conclusion: Using a computational phantom to monitor the dose to the sensitive organs (eye and skin) for personnel involved in the handling of ¹²⁵I seed sources can be an accurate and inexpensive method.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.46-53
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• 1996

Background: Endotoxin or lipopolysaccharide(LPS) can prime phagocytic cells such as polymorphonuclear leukocytes, monocytes or animal peritoneal macrophages to generate increased amounts of secretory products such as oxygen free radicals and tumor necrosis factor, which play an important role in developing adult respiratory distress syndrome in gram negative sepsis. Human alveolar macrophages(HAM) are continuously exposed to various stimuli inhaled into the alveoli, and the response to LPS might be different in HAM. Therefore, we investigated the effect of LPS pre-exposure on HAM adhered to plastic surface and A549 cell(type II human alveolar epithelial cell line) monolayer. Methods: HAM were isolated from bronchoalveolar lavage fluid from normal lung of the patients with localized lung cancer and esophageal cancer. LPS was exposed to HAM for 2hrs before or after adherence to plastic surface of 24-well Linbro plate and A549 cell monolayer. And then HAM was stimulated with PMA(phorbol myristate acetate) or fMLP(N-formyl-methionylleucyl-phenylalanine). The amount of hydrogen peroxide($H_2O_2$) production in the supernatant was measured on the principle of peroxidase-dependent oxidation of phenol red by hydrogen peroxide. Results: LPS pre-exposure could not enhance $H_2O_2$ production in neither HAM adhered to plastic surface nor one to A549 cell monolayer. But LPS even in the absence of PMA or fMLP stimulation directly increased $H_2O_2$ release in HAM if added after the adherence to A549 cell monolayer. Conclusion: Endotoxin does not prime HAM, but may directly activate HAM adhered to alveolar epithelial cells. Further investagation will be necessary.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.1-11
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• 2006

Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.