• Biomolecules & Therapeutics
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• 제21권4호
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• pp.264-269
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• 2013

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• 한국자원식물학회지
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• 제28권3호
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• pp.333-340
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• 2015

This study measured the plasma and liver concentrations of cytokines, the distribution of blood lymphocyte subpopulations (CD4 and CD8), plasma levels of nitrite (NO₃^–) and nitrate (NO₂^–), intercellular adhesion molecule 1 (ICAM-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), prostaglandin E2 (PGE2), and peritoneal lavage fluid (PLF) levels of monocyte chemotactic protein 1 (MCP-1) and CINC-1 in order to examine the anti-inflammatory activity of the cinnamon extract in lipopolysaccharide (LPS)-exposed rats. The plasma concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) were lower in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection. Furthermore, the liver concentrations of IL-1β, IL-6, and TNF-α were lower in the cinnamon extract groups than in the control group at 5 h after LPS injection. Plasma IL-10 concentrations were higher in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection, and liver concentrations of IL-10 did not differ significantly among all treatment groups at 5 h after LPS injection. The distribution of CD4 tended to increase, and that of CD8 tended to decrease in the cinnamon extract groups. The CD4/CD8 ratio was increased in the cinnamon extract groups. The plasma concentrations of NO₃^–/NO₂^–, ICAM-1, CINC-1, and PGE2 and the PLF concentrations of MCP-1 and CINC-1 exhibited a tendency to decrease in the cinnamon extract groups. These results indicate that cinnamon extract can exert functional anti-inflammatory effects.

• 사상체질의학회지
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• 제12권2호
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• pp.171-183
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• 2000

1. Back ground and purpose An experimental study has done to examine the effect of defense and cure gastric mucasal damage of Mokdan-pijihwang-tang. 2. Methods Mice had intragastric injected with MJ extract before indomethacin treatment which induces homorrhage infarct and erosion artificially. Degree of lipid peroxidation, general morphology, change of mucous cell, the distribution of PNA, ICAM and distribution of apoptotic cell were objected. (Abbreviation) MJ : Mokdanpijihwang-tang, PNA : Peanut Agglutinin, ICAM : Intercellular Adhesion Molecule 3 Results 1) The degree of lipid peroxidation in INDO-group had increased conspicuously than control group. But the degree of lipid peroxidation in MJ-group had decreased than INDO-group and these decline had probability. 2) After indomethacin treatment, hemorrhage infarct and erosion had increased in stomach body. But in MJ-group, the configuration is normal, except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 3) Surface mucous cell and neck mucous had disappeared in INDO-group. But in MJ-group tormal distribution had shown like control group except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 4) PNA positive reaction had not shown in INDO-group. But medium PNA positive reaction had shown In Mj-group. 5) ICAM positive reacted cell had shown in INDO-group. The decrease of ICAM positive cell were shown than INDO-group. 6) A number of apoptotic cell was distributed in hemorrhagic erosion. A few number of apoptotic cell was distributed in MJ-group except some surface mucous. 4. Conclusion These results suggest that MJ has an effect on cure of gastric mucosal damage.

• 동의생리병리학회지
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• 제25권2호
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• pp.270-274
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• 2011

The prevalence of atopic dermatitis has markedly increased in recent years but the mechanism has not been clearly revealed. Recent study exhibited that atopic dermatitis was exacerbated by the increase of proteinase-activated receptor (PAR)-2 expression, which activated $I{\kappa}B$ kinase --> nuclear factor kappa B. Therefore, we determined whether the allergens of dust mites induced the expression of PAR-2, intercellular adhesion molecule-1 (ICAM-1, adehision molecule), interleukins (IL)-6 in HaCaT keratocytes and which herbal 1,3-butylene glycol extracts (Mori Cortex Radicis, Sanguisorba officinalis L., Arctium lappa Linne, Torilis japonica DC, Melia azedarach Linne var. japoinca Makino) suppressed their expression. Dust mite allergen increased PAR-2, ICAM-1 and IL-6 expression in HaCaT cells in a dose-dependent manner up to $3{\mu}g/mL$ but their expression reached the plateau over the dosages. The allergen ($3{\mu}g/mL$) also secreted more cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and IL-6 into the media. Among five different herbal extracts ($50{\mu}g/mL$), Mori Cortex Radicis and Sanguisorba officinalis L. suppressed the PAR-2, ICAM-1 and IL-6 expression in HaCaT cells, which was activated by dust mite allergen ($3{\mu}g/mL$) and they also reduced the secretion of TNF-${\alpha}$ and IL-6 into the media. In conclusion, Mori Cortex Radicis and Sanguisorba officinalis L. can effectively reduce the prevalence and progression of atopic dermatitis by dute mite allergen.

• Nutrition Research and Practice
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• 제7권4호
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• pp.302-308
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• 2013

The emerging role of endothelial inflammation in diabetes has stimulated research interest in the effects of nutrition on related indices. In the current study we investigated whether the nutrient composition of dietary formula as reflected in glycemic index (GI) may be predictive of postprandial endothelial inflammation in non-diabetic subjects. A double-blinded, randomized, crossover study was conducted in non-diabetic subjects (n = 8/group). Each subject consumed three types of diabetes-specific dietary formulas (high-fiber formula [FF], high-monounsaturated fatty acid (MUFA) formula [MF] and control formula [CF]) standardized to 50 g of available carbohydrates with a 1-week interval between each. The mean glycemic index (GI) was calculated and 3-hour postprandial responses of insulin, soluble intercellular adhesion molecule-1 (sICAM-1), nitrotyrosine (NT) and free fatty acids (FFA) were measured. The MF showed the lowest mean GI and significantly low area under the curve (AUC) for insulin (P = 0.038), but significantly high AUCs for sICAM-1 (P<0.001) and FFA (P < 0.001) as compared to the CF and FF. The FF showed intermediate mean GI, but significantly low AUC for NT (P<0.001) as compared to the CF and MF. The mean GI was not positively correlated to any of the inflammatory markers evaluated, and in fact negatively correlated to changes in FFA (r = -0.473, P = 0.006). While the MF with the lowest GI showed the highest values in most of the inflammatory markers measured, the FF with intermediate GI had a modest beneficial effect on endothelial inflammation. These results suggest that nutrient composition of dietary formula as reflected in the GI may differently influence acute postprandial inflammation in non-diabetic subjects.

• Kidney Research and Clinical Practice
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• 제37권4호
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• pp.404-413
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• 2018

Background: Dynapenic obesity and sarcopenic obesity increase cardiovascular disease (CVD) and mortality in nonuremic patients. The present study was designed to determine the prevalence of dynapenic obesity and sarcopenic obesity and their associations with CVD risk factors in peritoneal dialysis (PD) patients. Methods: All eligible PD patients in Tehran peritoneal dialysis centers were included in this cross-sectional study. Skeletal muscle mass and fat mass were assessed using bioelectrical impedance analysis. Muscle strength and physical performance were determined using hand grip strength and a 4-meter walk gait speed test, respectively. In addition, a 5-mL blood sample was obtained from each patient. Results: The prevalence of dynapenic obesity and sarcopenic obesity were 11.4% and 3.8% in PD patients, respectively. Serum high-sensitive C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1, triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly higher in PD patients with dynapenic obesity than in dynapenic nonobese and nondynapenic nonobese patients. Similarly, serum concentrations of CVD risk factors in PD patients with sarcopenic obesity were higher than in nonsarcopenic nonobese patients, but these differences were statistically significant only for serum hs-CRP and triglyceride. In addition, muscle strength and skeletal muscle mass percentage were negatively associated with markers of inflammation and dyslipidemia, whereas body fat percentage was positively associated with these CVD risk factors. Conclusion: This study indicates that although the prevalence of dynapenic obesity and sarcopenic obesity are relatively low in PD patients, these disorders may be associated with CVD risk factors.

• IMMUNE NETWORK
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• 제23권5호
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• pp.42.1-42.21
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• 2023

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wildtype (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4369-4376
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• 2015

Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma.

• Journal of Gastric Cancer
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• 제1권2호
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• pp.92-99
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• 2001

Purpose: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated $\beta$-catenin disrupts the interaction between E-cadherin and $\alpha$-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, $\beta$-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. Materials and Methods: The patterns of E-cadherin, $\beta$-catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. Results: Increased expressions of E-cadherin, $\beta$-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the $\beta$-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). Conclusion: In gastric cancers, reduced expressions of the E-cadherin, $\beta$-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.