• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.3
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• pp.12-27
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• 2014

Objectives: This study was performed to evaluate the effect of Guibi-tang water extract (GB) on osteoporosis. Methods: We examined the effect of GB on osteoclast differentiation using murine pre-osteoclastic RAW 264.7 cells treated with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect of GB on osteoclast was measured by counting TRAP (+) multinucleated cells and measuring TRAP activity. The mRNA expressions of osteoclastogenesis-related genes (Cathepsin K, MMP-9, TRAP, NFATc1, MITF, TNF-${\alpha}$, IL-6, COX-2) were measured by real-time PCR. We examined the effect of GB on osteoblast proliferation, ALP activity, bone matrix protein synthesis and collagen synthesis using murine calvarial cell. Results: GB decreased the number of TRAP (+) multinucleated cells and inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. GB decreased the expression of genes related osteoclastogenesis such as Cathepsin K, MMP-9, TRAP, NFATc1, MITF, COX-2 in RANKL-stimulated RAW 264.7 cell. But GB did not decrease the expression of iNOS and increased the expression of TNF-${\alpha}$, IL-6 in RANKL-stimulated RAW 264.7 cell. These genes (iNOS, TNF-${\alpha}$, IL-6) are thought to be related with the inflammatory bone destruction. GB increased cell proliferation of rat calvarial cell and also increased ALP activity in rat calvarial cell. GB did not increase bone matrix protein synthesis but increased collagen synthesis in rat calvarial cell. Conclusions: This study suggests that GB may be effective in treating osteoporosis by inhibiting osteoclast differentiation and its related gene expression and by increasing osteoblast proliferation.

• Journal of the Korea Computer Graphics Society
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• v.28 no.1
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• pp.1-9
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• 2022

Non-small cell lung cancer (NSCLC) accounts for a high proportion of 85% among all lung cancer and has a significantly higher mortality rate (22.7%) compared to other cancers. Therefore, it is very important to predict the prognosis after surgery in patients with non-small cell lung cancer. In this study, the types of preoperative chest CT image patches for non-small cell lung cancer patients with tumor as a region of interest are diversified into five types according to tumor-related information, and performance of single classifier model, ensemble classifier model with soft-voting method, and ensemble classifier model using 3 input channels for combination of three different patches using pre-trained ResNet and EfficientNet CNN networks are analyzed through misclassification cases and Grad-CAM visualization. As a result of the experiment, the ResNet152 single model and the EfficientNet-b7 single model trained on the peritumoral patch showed accuracy of 87.93% and 81.03%, respectively. In addition, ResNet152 ensemble model using the image, peritumoral, and shape-focused intratumoral patches which were placed in each input channels showed stable performance with an accuracy of 87.93%. Also, EfficientNet-b7 ensemble classifier model with soft-voting method using the image and peritumoral patches showed accuracy of 84.48%.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3865-3869
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• 2016

Curcumin, a polyphenolic compound isolated from the rhizomes of an herbaceous perennial plant, Curcuma longa, is known to possess anticancerous activity. However, the mechanism of apoptosis induction in cancers differs. In this study, we have (1) investigated the anticancerous activity of curcumin on REH and RS4;11 leukemia cells and (2) studied the chemo-sensitizing potential of curcumin for doxorubicin, a drug presently used for leukemia treatment. It was found that curcumin induced a dose dependent decrease in cell viability because of apoptosis induction as visualized by annexin V-FITC/ PI staining. Curcumin-induced apoptosis of leukemia cells was mediated by PARP-1 cleavage. An increased level of caspase-3, apoptosis inducing factor (AIF), cleaved PARP-1 and decreased level of Bcl2 was observed in leukemia cells after 24h of curcumin treatment. In addition, curcumin at doses lower than the $IC_{50}$ value significantly enhanced doxorubicin induced cell death. Therefore, we conclude that curcumin induces apoptosis in leukemia cells via PARP-1 mediated caspase-3 dependent pathway and further may act as a potential chemo-sensitizing agent for doxorubicin. Our study highlights the chemo-preventive and chemo-sensitizing role of curcumin.

• Journal of Food Hygiene and Safety
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• v.12 no.3
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• pp.188-194
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• 1997

The growth inhibition effect of Orally administrated yogurt ACE and Metchnikoffupon E. coli O157:H7 and S. typhimurium inoculated into gastric lumen of rabbits was in vestigated. The rabbits challenged with each 1 $m\ell$ of suspension containing 108 CFU/$m\ell$ of the pathogens were divided into 4 groups by the interval of yogurt administration: A group; preadministrated 7 days before inoculation of the pathogens and fed daily; B group; administrated daily after inocjlation of the pathogens, C group; administrated every 3 days after inoculation of the pathogens; Control group, not fed after inoculation of the pathogens. Each 3 $m\ell$ of yogurt containing 109 CFU/$m\ell$ was orally administrated into rabbits. All yogurt administrated groups (A, B, c) chowed growth ingibition effect on E. coli O157:H7 in one day after inoculation of the pathogen by the level of 0.8~1.0 log CFU/g, compared with the result differences between the control group and the yogurt administrated groups. In the control group after 5 days of inoculation, the number of colonized pathogens was 105~106 CFU/g, whereas 103~104 CFU/g was detected in the yogurt administrated groups. After 10 days of inoculation, the viable pathogen number per gram (g) of the rabbit feces was 103 CFU/g in the control group, whereas the number below 101 CFU/g was detected in the group A, and 102 CFU/g in the control group, B and C. The growth inhibition effect of yogurt administration on E. coli O157:H7 was highly increased in the order of A, B, and C group. The same effect on S. typhimurium was observed at the level of 2 log CFU/g in the Metchnikoff yogurt administrated groups, compared with the control group result in one day after inoculation of the pathogen. In 7 days after inoculation of the pathogen, the viable number was increasingly decreased, and finally after 15 days no viable cell of S. typhimurium was discharged into the fecal samples in the group A, and the mean level of 10* CFU/g was detected in the group B, but there was no growth inhibition effect in the group C. The growth inhibition effect on S. typhimurium was observed at the same level of viable cell number between the yogurt ACE administrated groups and the control group in 5 days after inoculation. But, after 10 days of inoclation the viable cell number was started to decrease, and the viable cell of S. typhimurium was not discharged from rabbit intestinal contents after 15 days of inoculation in the yogurt ACE administrated groups. In such a case that yogurt was administrated in order to prevent the pathogens, pre-administration on a daily basis one week before inoculation of the pathogens exerted considerable effect in growth inhibition. In comparison with two kinds of yogurt tested in this study, the growth inhibition effect on two kinds of pathogens was observed more highly in the Metchnikoff administated group than the ACE administrated group.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.166-179
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• 2000

Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.449-458
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• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Journal of Life Science
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• v.19 no.10
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• pp.1396-1402
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• 2009

Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of $PGE_2$ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of $PGE_2$ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and $PGE_2$ production, we examined the activation of nuclear factor-kappaB (NF-$\kappa$B) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-$\kappa$B. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.

• Journal of Oriental Neuropsychiatry
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• v.24 no.3
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• pp.309-320
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• 2013

Objectives : There is a possibility LRE as remedy in Alzheimer disease (AD), but it's nerve protection effect and mechanism have to be elucidate. In this research, we applied LRE on $A{\beta}_{25-35}$ pre-treated SH-SY5Y cells, to find out the nerve protection effect and mechanism in AD cell model. Methods : We tried to confirm that effect by experimenting with 20, 50, and $100{\mu}g/ml$ concentration of LRE as a medicine. Next experiment, we assessed damage effect which induced $A{\beta}_{25-35}$, known to cause AD, on SH-SY5Y cell. In addition, cellular viability test is executed under $H_2O_2$ treatment condition in a SH-SY5Y cell. Results : 1. In $A{\beta}_{25-35}$ treated SH-SY5Y cell, LRE exhibited an anti-phosphorylation effect about tau protein, JNK, and IKB. 2. LRE prevent nerve cell apoptosis, which indued $A{\beta}_{25-35}$ and oxidative stress, modify JNK engaged synaptic structure and $NF{\kappa}B$ induced p75-neurotrophin receptor polymorphism. Conclusions : We found that LRE prevented oxidative stress-induced cellular destruction, for example, increased SOD activity of $A{\beta}_{25-35}$ treated SH-SY5Y cell and reduced toxicity of oxygen free radical. Consequently, the ingredients of LRE have a role as a catalyzer for $A{\beta}_{25-35}$ clearance and as scavenger for active oxygen free radical.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.147-154
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• 2022

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca²⁺ entry (SOCE)-related proteins and intracellular Ca²⁺ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca²⁺ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca²⁺. Moreover, extracellular Ca²⁺ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca²⁺. Conclusion: Extracellular Ca²⁺ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca²⁺ is essential for determining anti-cancer drug efficacy.