• 한국식물병리학회:학술대회논문집
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• 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
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• pp.82-83
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• 2003

Plants have evolved differently from animals having mobile activities. Thus, plants should have developed unique defense mechanisms against biotic/abiotic stresses to which plants are differently exposed, according to seasons. Most organisms have an conserved signaling network using mitogen-activated protein kinase (MAPK) cascade(s). The phenomenon implied that they are functionally very important in all organisms. In fact, they constitute one of the major components of signaling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. Recently, complete MAPK cascade was first characterized in Arabidopsis from the receptor kinase (FLS2) through fellowing MEKKI -MKK4/MKK5-MPK3/MPK6-WRKY22/MRKY29 pathway. Whereas, MAPK cascade signaling pathway in monocot plant including rice (0ryza sativa L.), the most important of all food crops and an established monocot plant research model, MAPKinase kinase kinases (MAPKKK) of rice are the first upstream component of the MAPK cascade, but MAPKKK has been first identified and characterized in our lab and designated as, OsEDRl based on its homology with the Arabidopsis EDRI. The Arabidopsis EDRl was regarded as a negative regulator of defense response and the role of rice OsEDRl was analyzed. Transcriptional regulation of OsEDRl was detected under various stresses and immunoblotting analysis is going on to detect the level of OsEDRl protein in the mutants showing unique phenotype. We also introduced the constitutively active and the dominant negative forms of the OsEDRl for characterizing biological function.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Parasites, Hosts and Diseases
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• 제55권5호
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• pp.491-503
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• 2017

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine ($5{\mu}M$) at $20{\mu}M$ and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at $1-5{\mu}M$, but host cells were destroyed at $10-20{\mu}M$. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

• International Journal of Heart Failure
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• 제6권3호
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• pp.129-136
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• 2024

Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions: Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

• Molecules and Cells
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• 제39권2호
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• pp.119-128
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• 2016

Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-$3{\beta}$ activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1991년도 제25차 학술대회 연제순서 및 초록
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• pp.14-14
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• 1991

후두의 생리적 기능은 하기도를 보호하는 방어기능과 호흡기능 그리고 발성기능으로 대별할 수 있는데 이 가운데 계통발생적으로 가장 원시적이지만 중요한 기능은 하기도 방어기능으로 이는 다른 기능과 달리 전적으로 불수의적이고 반사적으로 이루어진다. 이 기능은 후두내 점막에 존재하는 촉각 수용체(tactile receptor)가 자극되면서 후두근육이 수축 반사를 일으켜 성문이 닫히는 성문폐쇄반사(glottic closure reflex)로서 다접합뇌간반사(polysynaptic brain stem response)이다. 현재까지 후두의 신경장애에서 그 부위나 정도 또는 신경재생 상태 등을 검사하는 방법으로 근전도검사가 주로 쓰여져 왔으나 그것이 주는 정보가 극히 제한되어 있다. 그러나 최근 청각뇌간유발반응과 같이 후두뇌간유발반응 이라 명명된 wave가 존재한다는 사실이 밝혀져 이에 대한 연구가 이루어지고 있어 이것이 임상에 쓰여질 수 있다면 현재 성문폐쇄반사의 소실이나 이상이 원인으로 사료되는 idiopathic laryngospasm, gastroesophageal reflux, spastic dysphonia, stuttering, sudden infant death syndrome과 같은 질환의 진단과 치료에 커다란 진전이 있을 것이다. 이에 저자들은 고양이 6마리를 이용하여 상후두신경을 전기적으로 자극하여 유발되는 반응을 far field recording을 이용 평균 가산법으로 그 wave를 측정하여 다음과 같은 결과를 얻었다. 1. 상후두신경자극(2㎃, stimuli frequency 3/s, Band filter 320-1000, 0.2 ㎳ duration)에 의한 반회신경에의 유발 반응을 기록하였고 그 잠복시간은 평균 8.2 ㎳ 였다. 2. 상후두신경을 자극하여 후두뇌간유발반응을 기록하였고 후두뇌간유발반응은 4개의 양 wave와 4개의 음 wave로 구성되었다. 3. 각 wave의 평균 잠복시간은 P1은 0.8㎳, P2는 2.3㎳, P3는 3.6㎳, P4는 4.3㎳였고 N1은 1.5㎳, N2 은 2.7㎳, N3는 3.9㎳, N4는 5.5㎳ 였다.

• Clinical and Experimental Pediatrics
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• 제53권5호
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• pp.616-622
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• 2010

Enterovirus 71 (EV71) has been recognized as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with severe neurological symptoms. In the spring of 2009, HFMD was epidemic in Korea. Severe cases with complication, including death, have been reported and it has become a public health issue. Most symptomatic EV71 infections commonly result in HFMD or herpangina. These clinical manifestations can be associated with neurologic syndromes frequently. Neurologic syndromes observed in EV71 include meningitis, meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barr$\acute{e}$ syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome, benign intracranial hypertension, and brainstem encephalitis. Examinations for EV 71 were performed from the stools, respiratory secretion or CSF of the children by realtime PCR. Gene analysis showed that most of them were caused by EV71 subgenotype C4a which was prevalent in China, 2008. Public health measures including personal and environmental hygiene, must to target daycare centers, kindergartens, and schools where highly susceptible children congregate. To prevent the spread of infection, preschools where transmission persists for more than 2 incubation periods, have been recommended for closure, and trigger criteria for voluntary closure was instituted. During closure, operators are to thoroughly clean the centers before they are allowed to reopen. In addition, parents are advised to ensure that their children adopt a high standard of personal hygiene and to keep the infected child at home until full recovery. Because the outbreaks occur in a cyclical pattern, surveillance system to predict next outbreaks and adequate public health measures to control need to be planned for future. Control of EV71 epidemics through surveillance and public health intervention needs to be maintained in Korea. Future research should focus on understanding of EV71 virulence, identification of the receptor(s) for EV71, development of antiviral agents and development of vaccine.

• 생명과학회지
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• 제22권5호
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• pp.697-701
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• 2012

본 연구에서는 항응고제로서의 역할을 가지면서 또한 혈액응고와는 관련 없는 종양세포의 전이 등을 조절하는 것으로 알려진 activated protein C (APC)가 종양세포의 사멸에는 어떠한 영향을 미치는 지에 대한 연구를 수행하였다. Tumor necrosis factor (TNF)-${\alpha}$와 cyclohexamide를 병합 처리하거나 FAS를 처리하게 되면 인간 신장암세포인 Caki에서는 유의적인 세포사멸이 일어난다. 하지만, APC는 이러한 세포사멸에 아무런 영향을 미치지 못하였다. 또한 TRAIL을 인간 뇌 암세포인 T98G와 유방암세포인 MDA231세포에 처리하여 세포사멸을 일으켰을 때에도 APC는 세포사멸을 조절하지 못하였다. 그러나, TRAIL에 대한 민감도를 증가시키기 위한 kahweol과 TRAIL의 병합처리나, kahweol과 malatonin의 병합처리에 의한 신장암세포의 사멸은 APC에 의해 유의적으로 억제되는 것을 확인하였다. 따라서, 이는 APC가 항암치료의 효율성을 조절 할 수 있는 가능성을 가짐을 의미한다.

• 한국식품영양과학회지
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• 제44권5호
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• pp.649-656
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• 2015

무지개송어 아가미상피세포를 이용하여 cortisol에 의해 유도된 세포 손상에 대항하는 아연의 보호 효과를 연구하였다. 24시간 동안 cortisol에 노출된 세포들은 농도 의존적으로 LDH 방출이 증가하였고, 세포 생존율은 감소하였다. 아연($100{\mu}M$ $ZnSO_4$) 처리에 의해 이와 같은 영향이 감소하였고, 아연은 cortisol에 의해 유도된 caspage-3 활성, 즉 apoptosis에 대항하여 세포를 보호하였다. Cortisol에 의해 유도된 세포 사멸, LDH 방출과 caspase-3 활성은 glucocorticoid 수용체의 길항제인 Mifepristone(RU-486) 처리에 의해 차단되었는데, 이것은 세포 손상이 cortisol과 관련이 있다는 것을 제안하였다. 더하여 cortisol에 의해 유도된 세포 손상 모델에서 MT, GST 그리고 G6PD와 같은 항산화 유전자 발현에 대한 아연의 영향을 연구했다. MTA, MTB, GST 그리고 G6PD mRNA 수준은 아연과 cortisol을 각각 단독 처리에 의해 그리고 아연과 cortisol을 동시 처리에 의해 증가하였다. 이와 같은 증가는 아연이나 cortisol 단독 처리보다는 $100{\mu}M$ $ZnSO_4$와 $1{\mu}M$ cortisol을 동시에 처리했을 때 MTA, MTB, GST 그리고 G6PD mRNA 수준이 더 높았다. 아연 처리에 의해 세포 내 자유 아연 농도가 증가하였고, 이와 같은 반응은 cortisol과 아연을 함께 처리했을 때 세포 내 자유 아연 농도가 더 증가하였다. 결론적으로 아연 처리는 간접적인 항산화 활성을 통해 cortisol에 의해 유도 세포독성 및 apoptosis를 저해하였다.

• 한국자원식물학회지
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• 제33권4호
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• pp.279-286
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• 2020

본 연구에서는 부처꽃 에탄올 추출물(ELM)에 대한 항암효능을 알아보기 위하여 인체백혈병 U937 세포의 증식에 미치는 영향과 이와 연관된 apoptosis 유발 여부와 함께 그에 따른 분자생물학적 기전에 대해서 조사하였다. 먼저 ELM 처리에 따른 증식 억제 정도를 조사한 결과, ELM 처리 농도 의존적으로 생존율 및 증식억제 현상이 나타났으며, 핵의 형태 변화, DNA 단편화 및 apoptosis 유발에 관하여 조사한 결과 역시 ELM 처리 농도 의존적으로 증가됨을 확인할 수 있었다. ELM 처리에 따른 U937 세포에서의 apoptosis 유발에 있어서 미토콘드리아 막의 기능 손상이 관여하는 지를 확인하기 위하여 MMP의 변화 정도를 확인한 결과, ELM 처리 농도 증가에 따라 MMP의 소실이 증가하는 것을 관찰할 수 있었다. 이러한 MMP의 소실에 가 관여하는 지를 확인하기 위하여 사멸수용체(DR4, 5, Fas) 및 사멸수용체에 결합하는 리간드(FasL, TRAIL)의 발현 변화를 확인한 결과, DR4 및 DR5의 발현이 증가하는 것으로 관찰되었다. 또한 내인적 경로에 관여하는 Bcl-2 family 유전자들의 발현변화를 확인한 결과, Bcl-2 발현 감소 및 Bax의 발현 증가의 변화를 보였으며, Bid 단백질의 발현감소가 나타났으므로 상대적으로 tBid의 생성이 증가되었음을 추측할 수 있었다. 한편apoptosis 유발에 직접적으로 관여하는 것으로 알려진 caspase-3, -8 및 -9의 발현에 미치는 ELM의 영향에 대해서 조사하였다. 결과에서 알 수 있듯이 ELM은 death receptor에 의하여 활성화 되는 것으로 알려진 caspase-8 및 세포질로 방출된 cytochrome c에 의하여 활성화 되는 것으로 알려진 caspase-9의 활성화를 유발하였으며, caspase cascade에 의하여 apoptosis에 직접적으로 관여하는 caspase-3의 발현도 증가시키는 것으로 나타났다. 또한 활성화된 caspase-3에 의하여 분해가 일어나는 기질 단백질인 PARP의 경우 ELM 처리에 의하여 모두 단편화가 유발되는 것으로 나타났다. 이상의 결과를 종합해 보면 인체 백혈병 U937 세포에 ELM을 처리하였을 경우에 유발되는 apoptosis는 외인적 경로인 DR4 및 DR5의 발현 증가를 통한 caspase-8의 활성화와 이로 인한 Bid 단백질의 단편화와 함께 내인적 경로의 미토콘드리아 기능 손실에 의하여 caspase-9 및 -3의 활성화 유발과 기질단백질들의 분해가 중요한 역할을 하는 것으로 생각되며, IAP family의 발현 감소로 인하여 caspase의 활성이 억제되지 못하는 것도 apoptosis 유도에 어느 정도 관여했을 것으로 생각된다. 따라서 ELM 처리에 의하여 유발되는 apoptosis는 외인적 경로 및 내인적 경로를 모두 경유하는 multiple apoptotic pathway에 의하여 조절되며, 이때 caspases가 중요한 역할을 한다는 것을 알 수 있었다.