• Biomolecules & Therapeutics
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• 제26권2호
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• pp.175-181
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• 2018

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

• 가정간호학회지
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• 제25권3호
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• pp.204-214
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• 2018

Purpose: This study aimed conducted to investigate biomedical ethics awareness and attitudes toward dignified death and advance directives among nursing students. Methods: Data were collected through structured questionnaires from 222 nursing students with clinical practice experience, from November 7 to 23, 2015. Data were analyzed by independent t-tests, one-way ANOVA, Kruskal-Wallis test, and Pearson's correlation coefficients using SPSS WIN 22.0. Results: The scores for biomedical ethics awareness and attitudes toward dignified death were 2.89 and 3.15, respectively. Regarding attitudes toward advance directives (ADs), most students agreed with writing ADs. The main reason given for writing ADs is "I want to receive my treatment of choice." As for the range and explanation method for ADs, 45.7% of participants responded, "do not know well." Regarding willingness toward life sustaining treatment, "only pain control, no life sustaining treatment" was indicated by 83.4% and, "all information about symptoms and prognosis" by 91.9% of participants. For willingness to write ADs, 70.0% of participants responded "yes." Conclusion: Curriculum for nursing ethics should be included in clinical training courses to improve related courses and provide an opportunity to deal with practical problems, such as biomedical ethics, death with dignity, and ADs.

• Journal of Ginseng Research
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• 제34권2호
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• pp.138-144
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• 2010

Ginseng (Panax ginseng C.A. Meyer) has been shown to have anti-stress effects in animal studies. However, most studies have only managed to detect altered levels of biomarkers or enzymes in blood or tissue, and the actual molecular mechanisms by which ginseng exerts these effects remain unknown. In this study, the anti-oxidative effect of Korean red ginseng (KRG) was examined in human SK-N-SH neuroblastoma cells. Incubation of SK-N-SH cells with the oxidative stressor hydrogen peroxide resulted in significant induction of cell death. In contrast, pre-treatment of cells with KRG decreased cell death significantly. To elucidate underlying mechanisms by which KRG inhibited cell death, the expression of apoptosis-related proteins was examined by Western blot analysis. KRG pre-treatment decreased the expression of the pro-apoptotic gene caspase-3, whereas it increased expression of the anti-apoptotic gene Bcl-2. Consistent with this, immunoblot analysis showed that pre-treatment of the SK-N-SH cells with KRG inhibited expression of the pro-inflammatory gene cyclooxygenase 2 (COX-2). RT-PCR analysis revealed that the repression of COX-2 expression by KRG pre-treatment occurred at the mRNA level. Taken together, our data indicate that KRG can protect against oxidative stress-induced neuronal cell death by repressing genes that mediate apoptosis and inflammation.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.413-422
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• 2020

Delphinidin is a major anthocyanidin compound found in various vegetables and fruits. It has anti-oxidant, anti-inflammatory, and various other biological activities. In this study we demonstrated the anti-cancer activity of delphinidin, which was related to autophagy, in radiation-exposed non-small cell lung cancer (NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxic dose of delphinidin (5 μM) before exposure to γ-ionising radiation (IR). We found that treatment with delphinidin or IR induced NSCLC cell death in vitro; however the combination of delphinidin pre-treatment and IR was more effective than either agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethal dose. Moreover, combined treatment with delphinidin and IR, enhanced apoptotic cell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway. Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increased the expression of autophagy-induced cell death associated-protein in radiation-exposed NSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidin pre-treatment in radiation-exposed NSCLC cells. Collectively, these results show that delphinidin acts as a radiation-sensitizing agent through autophagy induction and JNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

• 의료법학
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• 제13권1호
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• pp.125-153
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• 2012

The adult guardianship system has been introduced through amendments of Korean Civil Code for the first time in the March 2011(Act No. 10429, 7. 1. 2013. enforcement). The adult guardianship system has the main purposes to provide a lot of help vulnerable adults and elderly, and protect them on the welfare related with property act, treatment, care, etc. There could be a controversy about whether the protection Legal Guardian's consent(formerly known as the Mental Health Act) or permission of the Family Court(revised Civil Code) are required to, or the Mental Health Act should be revised, when mental patient will be hospitalized forcibly. The author proposes that mental patient with Adult guardians should be determined by Legal Guardian's consent and approval of the Family Court, but mental patient without Adult guardians could be determined by Legal Guardian's consent. The issue of Withdrawing of life-sustaining treatment could be occurred due to the aging society and the development of modern medicine, and this has provided difficult, various problems to mankind in Legal, ethical, and social welfare aspects. The need of Death with dignity law or Natural death law has been reduced for a revision of the Civil Code. Therefore, on the issue of Withdrawing of life-sustaining treatment, in the future, intervention of the court is necessary in accordance with the revised Civil Code Section, and Organ Transplantation Act and the brain death criteria may serve as an important criterion.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7159-7162
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• 2014

Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

• Journal of Trauma and Injury
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• 제23권2호
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• pp.75-82
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• 2010

Purpose: In Korea, trauma is the $3^{rd}$ most common cause of death. The trauma treatment system is divided into pre-hospital and hospital stages. Deaths occurring in the pre-hospital stage are 50% of the total death, and 20% of those are deaths that are preventable. Therefore, the purpose of our study is to calculate the preventable death rates caused by trauma in our current pre-hospital system, to analyze the appropriateness of the treatment of traumatized patients and to draw a conclusions about the problems we have. Methods: The study was done on traumatized patients who expired at the emergency department from January 1, 2005, to December 31, 2009, at the Korea University Medical Centers in Anam, Guro and Ansan. The data on the patients were reviewed retrospectively based on characteristics, conditions on admission and trauma severity. The patient's RTS (revised trauma score) and ISS (injury severity score) was calculated. Preventable death rate was calculated by TRISS (the trauma score-injury severity score). Results: A total of 168 patients were enrolled. All patients were intubated and underwent CPR. Of the total, 72% patients were male, and traffic accidents were the most common form of trauma (52.4%), falls being second (28.6%). Head injury, solitary or multiple, was the most common cause of death (55.4%). Thirty-eight (38, 22.6%) deaths were preventable. The 22.6% preventable death rate consisted of 15.5% potentially preventable and 7.1% definitely preventable deaths. Based on a logistic regression analysis, the relationship between the time intervals until transfusion and imaging and death was statistically significant in the hospital stage. In the pre-hospital stage, transit time from the site of the injury to the hospital showed a significant relationship with the mortality rate. Conclusion: One hundred sixty-eight (168) patients died of trauma at the 3 hospitals of Korea University Medical Center. The TRISS method was used to calculate the preventable death rate, with a result of 22.6%. The only factor that was significant related to the preventable death rate in the pre-hospital stage was the time from injury to hospital arrival, and the time intervals until transfusion and imaging were the two factors that showed significance in the hospital stage. Shortening the time of treatment in the field and transferring the patient to the hospital as quickly as possible is the most important life-saving step in the pre-hospital stage. In the hospital stage, the primary survey, resuscitation and diagnosis should proceed simultaneously.

• IMMUNE NETWORK
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• 제20권1호
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• pp.9.1-9.21
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• 2020

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

• 생명과학회지
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• 제26권12호
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• pp.1458-1465
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• 2016

본 연구는 oxidative stress에 의한 세포죽음 분석의 이상적인 모델로 사용되는 HT22세포를 이용하여 천문동 에탄올추출물의 glutamate에 의한 oxidative toxicity에 대한 신경보호 효과를 살펴보았다. 이를 위해 cell viability, lactate dehydrogenase (LDH), 그리고 세포죽음형태, reactive oxygen species (ROS), mitochondria membrane potential (MMP) 등에 대한 flow cytometry 및 Western blot분석을 이용하였다. 천문동 추출물의 처리는 cell viability 및 LDH분석에서 glutamate에 의한 cell toxicity를 저하시키며, 특히 apoptotic cell death를 현저히 감소시켰다. ROS 및 MMP분석 결과, 천문동 추출물은 ROS의 형성을 저하시키며 glutamate에 의해 저하된 MMP를 현저히 회복시켜 주었다. 이와 관련된 단백질 발현을 보면, 천문동 추출물은 PARP 및 HO-1의 발현을 억제하였다. 이상의 결과는 천문동 추출물이 HT22해마세포에서 ROS형성저해 및 MMP회복에 의해 세포죽음을 완화시켜 보호작용을 하는 것으로 사료되며 oxidative toxicity관련 질환에 적용 가능할 것으로 보여 진다.

• BMB Reports
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• 제50권9호
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• pp.466-471
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• 2017

The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.