• Journal of Gastric Cancer
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• v.17 no.2
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• pp.120-131
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• 2017

Purpose: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. Materials and Methods: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). Results: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. Conclusions: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.7-15
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• 2015

Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

• 한국과학기술학회:학술대회논문집
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• 2015.12a
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• pp.247-278
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• 2015

Recently, as DNR prevails more and more in Korea, discussions regarding meaningless medical life-sustaining-treatment (LST) intensified. Some of the Supreme Court decisions are even discussed in mass media, causing public debates. These cases tell us that, as life-sustaining medical technologies are highly developed, more sociological and policy-related analyses are needed on them. Firstly, this study will review 40 previous studies that analyze recent discussions in Korea about LST. Secondly, this study also shows that in bioethical and policy-related perspectives, governance about LST calls for a new implications regarding thanatoethics and thanatopolitics. In this new theoretical framework, death with dignity (DwD) can be understood as a process of giving back the thanatopower to the subject who chooses his way of ending based on his sound and free will. Thirdly, some of the new LST or resuscitation technologies such as automated external defibrillators (AED) are developed in RRI framework. However, if subjects themselves choose not to apply those technologies on them, as in the case of DNR (do not resuscitate) vows, meaning of developing such technologies are to be questioned. But currently such questions regarding the limitations of RRI are seldom asked. I argue that in order to properly apply RRI framework on existing technology, we also need to consider these points.

• Molecules and Cells
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• v.42 no.9
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• pp.672-685
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• 2019

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.427-438
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• 2022

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Tuberculosis and Respiratory Diseases
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• v.86 no.2
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• pp.82-93
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• 2023

Tuberculosis (TB) is a significant public health concern. Globally, TB is among the top 10 and the leading cause of death due to a single infectious agent. Providing standard anti-TB therapy for at least 6 months is recommended as one of the crucial strategies to control the TB epidemic. However, the long duration of TB treatment raised the issue of non-adherence. Non-adherence to TB therapy could negatively affect clinical and public health outcomes. Thus, directly observed therapy (DOT) has been introduced as a standard strategy to improve anti-TB medication adherence. Nonetheless, the DOT approach has been criticized due to inconvenience, stigma, reduced economic productivity, and reduced quality of life, which ultimately could complicate adherence issues. Apart from that, its effectiveness in improving anti-TB adherence is debatable. Therefore, digital technology could be an essential tool to enhance the implementation of DOT. Incorporating the health belief model (HBM) into digital technology can further increase its effectiveness in changing behavior and improving medication adherence. This article aimed to review the latest evidence regarding TB medication non-adherence, its associated factors, DOT's efficacy and its alternatives, and the use of digital technology and HBM in improving medication adherence. This paper used the narrative review methodology to analyze related articles to address the study objectives. Conventional DOT has several disadvantages in TB management. Integrating HBM in digital technology development is potentially effective in improving medication adherence. Digital technology provides an opportunity to improve medication adherence to overcome various issues related to DOT implementation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1663-1670
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• 2012

The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.

• Journal of Life Science
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• v.33 no.9
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• pp.713-723
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• 2023

Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.33-45
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• 2011

Heat shock protein 90 (Hsp90) is ATPase-directed molecular chaperon and affects survival of cancer cell. Inhibitory effect of Hsp90 by inducing cell cycle arrest and apoptosis in the cancer cell was reported. However, its role during oocyte maturation and early embryo development is very insufficient. In this study, we traced the effects of Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on meiotic maturation and early embryonic development in pigs. We also investigated several indicators of developmental potential, including structural integrity, gene expression (Hsp90-, cell cycle-, and apoptosis-related genes), and apoptosis, which are affected by 17-AAG. Then, we examined the roles of Hsp90 inhibitor on viability of primary cells in pigs. Porcine oocytes were cultured in the NCSU-23 medium with or without 17-AAG for 44 h. The proportion of GV arrested oocytes was significantly different between the 17-AAG treated and untreated group (78.2 vs 34.8%, p<0.05). After completion of meiotic maturation, the proportion of MII oocytes was lower in the 17-AAG treated group than in the control group (27.9 vs 71.0%, p<0.05). After IVF, the percentage of penetrated oocytes was significantly lower in the 17-AAG treated group (25.2%), resulting in lower normal pronucleus formation (2PN of 14.6%). Therefore, the inhibition of meiotic progression by Hsp90 inhibitor played a critical role in fertilization status. Porcine embryo were cultured in the PZM-3 medium with or without 17-AAG for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without 17-AAG. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 17-AAG treated group compared with control (7.5 vs 4.4, respectively). Blastocysts that developed in the 17-AAG treated group had low structural integrity and high apoptotic nuclei than those of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. The mRNA expressions of cell cycle-related genes were down-regulated in the 17-AAG treated group compared with control. Also, the expression of the pro-apoptotic gene Bax increased in 17-AAG treated group, whereas expression of the anti-apoptotic gene Bel-XL decreased. However, the expression of ER stress-related genes did not changed by 17-AAG. Cultured pESF cells were treated with or without 17-AAG and used for MIT assay. The results showed that viability of pESF cells were decreased by treatment of 17-AAG ($2{\mu}M$) for 24 hr. These results indicated that 17-AAG decreased cell proliferation and increased cell death. Expression patterns Hsp90 complex genes (Hsp70 and p23), cell cycle-related genes (cdc2 and cdc25c) and apoptosis-related genes (Bax and Bcl-XL) were significantly changed by using RT-PCR analysis. The spliced form of pXbp-1 product (pXbp-1s) was detected in the tunicamycin (TM) treated cells, but it is not detected in 17-AAG treated cells. In conclusion, Hsp90 appears to play a direct role in porcine early embryo developmental competence including structural integrity of blastocysts. Also, these results indicate that Hsp90 is closely associated with cell cycle- and apoptosis-related genes expression in developing porcine embryos.