건강한 성인에서 테고프라잔 속방형 및 서방형 제제의 다양한 조합에서의 약동학 특성을 예측하기 위한 집단 약동학 모델링

학위논문(석사) -- 서울대학교대학원 : 의과대학 협동과정 임상약리학전공, 2023. 8. 장인진.Introduction: Tegoprazan is a novel potassium-competitive acid blocker used to treat gastric acid-related disease. Although the currently approved dosage regimen of tegoprazan (50 mg once daily) is effective in treatment of gastric acid-related disease, stronger effect is required for patients with severe acid-related diseases. This study aimed to develop a population pharmacokinetic (PK) model of various combinations of tegoprazan immediate and delayed release (IR and DR) formulations in healthy subjects, and to evaluate and predict the PK of tegoprazan at the optimal ratio of the tegoprazan IR to DR formulations. Methods: A six-cohort, open-label, randomized, single- and multiple-dose study was performed to evaluate the PK of tegoprazan in healthy male subjects. Subjects in each cohort received various combinations of tegoprazan IR and DR formulations (50, 75, or 100 mg) with single or multiple oral doses once daily for 7-d. Blood samples were collected for 48 and 192 h following single and multiple oral dose of tegoprazan, respectively. A population PK model was developed for tegoprazan IR and DR formulation using the nonlinear mixed-effect modeling approach from Monolix software. A model-based simulation was performed to predict the PK of tegoprazan at dose of 50, 75 and 100 mg, using the optimal ratio of tegoprazan IR and DR, which was determined based on the results of a clinical study. Results: A 1,398 plasma concentrations from 42 subjects were included in the population PK analysis. A two-compartment model with simultaneous zero-order absorption with different lag times and a linear elimination model appropriately described the PKs of a combination of tegoprazan IR and DR formulation. The population mean estimates for the PK parameters were as follows: CL/F, 13.9 L/h; V1/F, 55.9 L; V2/F, 58.0 L; Tk0,IR, 0.4 h; Tk0,DR, 3.6 h; Tlag,IR, 0.2 h; and Tlag,DR, 1.2 h. The model was evaluated using bootstrap and visual prediction checks, which showed that it was robust and precise. Furthermore, the simulation results indicated that tegoprazan has a good linear PK profile. Conclusion: The developed population PK model appropriately described the concentration-time profiles of tegoprazan in healthy subjects, enhancing the understanding of the PK properties of tegoprazan and its DR formulation. Additionally, it has the potential to determine the optimal ratio of tegoprazan IR to DR formulations, which could significantly improve efficacy of tegoprazan. Consequently, a combination of tegoprazan IR and DR at a 1:1 ratio is expected to achieve sufficient gastric acid suppression.서론: 테고프라잔은 위식도 역류 질환과 같은 위산 관련 질환을 치료하기 위해 사용되는 새로운 포타슘 경쟁적 위산 분비 차단제이다. 현재 승인된 테고프라잔 50 mg 1일 1회 복용법은 위산 관련 질환의 치료에 효과적이지만, 중증 위산 관련 질환을 가진 환자들에게는 더 강력한 효과가 필요하다. 따라서 본 연구는 건강한 대상자에서 테고프라잔 속방형 및 서방형 제제의 다양한 조합의 집단 약동학 모델을 수립하여 최적의 비율에서의 테고프라잔의 약동학을 평가하고 예측하고자 한다. 방법: 건강한 성인 남성을 대상으로 테고프라잔의 약동학을 평가하기 위하여 6-코호트, 공개, 무작위배정, 단회 및 반복 투여 시험을 진행하다. 시험대상자들은 각 코호트 별로 테고프라잔 속방형 및 서방형 제제의 다양한 조합(50, 75, 100 mg)을 단회 또는 7일동안 1일 1회 반복 경구 투여하였다. 테고프라잔 단회 및 반복 경구 투여 후 최대 48시간 및 192시간까지 혈액 샘플이 수집되었다. 집단 약동학 모델은 테고프라잔 속방형 및 서방형 제형에 대해 모노릭스 소프트웨어(버전 2023R1)의 비선형 혼합 효과 모델링 접근법을 사용하여 개발되었다. 또한, 임상시험 결과를 바탕으로 선정된 최적의 속방형 및 서방형 제제의 비율에서 테고프라잔 50, 75, 100 mg의 약동학을 예측하기 위한 모델 기반 시뮬레이션을 수행하였다. 결과: 집단 약동학 분석을 위하여 총 42명의 시험대상자에서 1,398개의 혈장 농도가 포함되었다. 테고프라잔 속방형 및 서방형 제제의 다양한 조합의 약동학은 서로 다른 지연 시간을 가진 동시 0차 흡수와 선형 제거 모델로 이루어진 2구획 모델로 적절하게 설명되었다. 최종 모델로부터 측정된 약동학 파라미터들의 집단 대표 평균 값은 다음과 같다; 겉보기 청소율(CL/F): 13.9 L, 중심 구획의 겉보기 용적(V1/F): 55.9 L, 구획의 겉보기 용적(V2/F): 58.0 L, 속방형의 흡수 시간(Tk0,IR): 0.4 h, 서방형의 흡수 시간(Tk0,IR): 3.6 h, 속방형의 흡수 지연 시간(Tlag,IR): 0.2 h, 서방형의 흡수 지연 시간(Tlag,DR): 1.2 h. 모델은 bootstrap과 시각적 예측 검사(VPC)를 통해 평가되었으며, 그 결과 개발된 모델이 견고하고 정확한 것을 보여주었다. 또한 시뮬레이션 결과 테고프라잔은 선형 약동학 프로파일을 따르는 것으로 나타났다. 결론: 개발된 모델은 건강한 성인에서 테고프라잔의 시간별 농도-시간 프로파일을 잘 설명함으로써 테고프라잔 및 테고프라잔 서방형 제제의 약동학 특성에 대한 이해를 높일 수 있었다. 또한, 개발된 모델은 테고프라잔 속방형 및 서방형 조합의 최적 비율을 결정하는 잠재력을 가지고 있다. 결과적으로 1:1 비율의 테고프라잔 속방형과 서방형 제제는 충분한 위산 억제를 달성할 수 있을 것으로 기대된다.ABSTRACT i Table of Contents v List of Tables vii List of Figures ix List of Abbreviations xii Introduction 16 1. Study Background 16 2. Purpose of Research 20 Method 21 1. Study design and population 21 2. Plasma concentration analysis 25 3. Non-compartment PK analysis 25 4. Population PK model development 26 5. Covariate selection 28 6. Population PK model evaluation 29 7. Model-based simulation 30 Results 32 1. Study population of model dataset 32 2. PK analysis 33 3. Population PK model 39 4. Covariate selection 45 5. Model evaluation 45 6. Simulation of combination tegoprazan 50 Discussion 54 Conclusion 61 Supplementary Material 62 1. PK parameter after multiple administration 62 2. PD in clinical study 63 3. PK–PD relationship 70 4. Monolix macro code for struct the final PK model 72 5. Population PK model development process 74 6. Individual fitting plots for the final PK model 78 7. Basic goodness-of-fit plots of normal normalized prediction distribution errors for final model. 84 8. Expected response of tegoprazan using Emax model at 1:1 ratio of tegoprazan IR and DR formulation. 85 Bibliography 87 Abstract in Korean 92석

Sentence-BERT를 활용한 영어-한국어 전이 학습

학위논문(석사) -- 서울대학교대학원 : 인문대학 언어학과, 2022.2. 신효필.This study focuses on constructing a Korean Sentence-BERT model in a novel method, using student-teacher knowledge distillation. The limitations of BERT have been well explored in previous publications. BERT has proven to be ineffective in deriving sentence-level embeddings and not applicable in practical situations where large amounts of sentence-level embeddings are required, such as document classification and clustering. Sentence-BERT was developed to alleviate these issues and create a model that can derive sentence embeddings in an efficient and accurate manner. This study explores a transfer learning method in Sentence-BERT, which allows even low-resource language models to leverage the power of models trained in high-resource languages such as Korean. Using translated sentence pairs in the source and target languages, the student model learns to map the translated sentence to the same points in the vector space as the teacher model using a simple mean squared error loss method. In this experiment, an English model was used as the teacher model and a cross-linguistic model was used as the student model. To the knowledge of this author, no Korean Sentence-BERT model has been trained using this novel method to the date of publication of this paper. To conduct this knowledge distillation for Sentence-BERT, a large number of source and target language translated sentence pairs are needed. After collecting available datasets on the web, the data was augmented with crawled data from the web, which was then aligned using a novel method and then pre-processed for cleaning. This research evaluates the model trained on this data using the knowledge distillation method on sentence-level tasks and multilingual tasks. The model successfully performs well on all tasks, proving its wide applicability and cross-lingual abilities.본 연구는 student-teacher knowledge distillation 전이학습 비법을 사용하여 영어-한국어 Sentence-BERT 모델을 학습한다. BERT의 한계는 이전 발표된 많은 연구에서 잘 탐구되었다. BERT는 문장 단위의 임베딩을 도출하는 데 효과적이지 않으며 문서 분류 및 클러스터링과 같이 대량의 문장 임베딩이 필요한 실용적인 상황에서는 적용할 수 없는 것으로 입증되었다. Sentence-BERT는 이러한 문제를 완화하고 효율적이고 정확한 방식으로 문장 임베딩을 도출할 수 있는 모델을 만들기 위해 개발되었다. 본 연구에서는 한국어와 같은 저자원 언어 모델도 영어와 같은 고자원 언어로 훈련된 모델과 같은 성능을 보일 수 있는 Sentence-BERT의 전이 학습 방법을 살펴본다. 의 모델은 Source 언어와 Target 언어에서 번역된 문장 쌍을 사용하여 Mean Squared Error Loss를 통해서 번역된 문장을 Teacher 모델과 동일한 벡터 공간에 매핑한다. 이 실험에서는 영어 모델을 Teacher 모델로, Cross-lingual 모델을 Student 모델로 사용한다. 저자가 알기로는, 이 논문의 출판일까지 이 새로운 방법을 사용하여 학습된 한국어 Sentence-BERT 모델은 없다. Sentence-BERT에 대해 이러한 knowledge distillation을 수행하려면 많은 수의 소스 언어 및 대상 언어 번역 문장의 쌍이 필요하다. 웹에서 사용 가능한 데이터 세트를 수집한 후, 데이터는 웹에서 크롤링된 데이터로 증강되었고, 이 데이터를 새로운 방법을 사용하여 정렬한 이후에 전처리를 했다. 이 연구는 문장 단위 테스트 및 영어-한국어 테스트를 통해서 훈련된 모델을 평가했으며 모델의 광범위한 적용 가능성과 다국어 능력을 입증하였다.1. Introduction 1 1.1 Purpose of Research 2 2. Related Works 4 2.1 BERT 4 2.2 Sentence-BERT 8 2.3 Existing Korean SBERT Models 11 3. Multilingual Transfer Learning for SBERT 12 3.1 Training Architecture 12 3.2 Advantages to SBERT Knowledge Distillation 13 4. English and Korean Multilingual SBERT 15 4.1 Setup 15 4.2 Data 15 4.3 Training 22 4.4 Evaluation 23 4.5 Discussion 28 5. Model Analysis 29 6. Conclusion 33 Bibliography 35 Appendix 39 Abstract in Korean 48석

전기의 도시가스 수요 대체현상을 중심으로

학위논문 (석사) -- 서울대학교 대학원 : 행정대학원 공기업정책학과, 2020. 8. 구민교.에너지는 사용과정에서 전환손실이 불가피한데 석탄, 석유, 가스와 같은 1차에너지를 그대로 사용하는 경우와는 달리 최종에너지인 전기로 전환하여 사용하는 경우에는 투입한 1차에너지의 약 40%만 전기로 변환된다. 실제 국가 전체 에너지전환손실 중 약 95%는 전기화 과정에서 발생하고 있는 것으로 파악되어 높은 전기화 현상은 에너지효율 악화의 주범이라고 할 수 있다. 우리나라에서는 물가안정과 산업경쟁력을 위해 정책적으로 전기요금이 낮게 유지되어 왔는데 결국 상대적으로 낮은 전기요금은 전기와 경쟁관계에 있는 다른 에너지원의 수요를 전기수요로 대체되도록 함으로써 전기 소비량을 증가시켜 왔으며, 특히 이러한 수요대체 현상은 도시가스와의 관계에서 두드러지고 있다. 에너지전환효율이 낮은 전기소비의 증가는 결국 전기 생산을 위해 더 많은 발전원료를 외국에서 수입해야 하므로 국가적 손실일 뿐만 아니라 기존에 구축되어 있는 1차에너지 공급인프라 외에 전기수요 증가에 대응하기 위하여 추가로 전력설비를 투자해야하므로 중복투자의 비효율도 발생한다. 본 연구는상대적으로 낮은 전기요금이 정말로 국가 전체의 에너지효율을 악화시키는가?라는 물음에 답하기 위하여 전기와 가스 간 상대가격 변동이 수요대체를 통하여 국가 에너지효율에 영향을 미치는지 실증분석을 통해 검증해 보고자 하였다. 검증을 위해 가스·전기 상대가격과 에너지전환효율(최종에너지소비/1차에너지공급)을 각각 독립변수와 종속변수로 설정하고, 2003년 1월부터 2018년 12월까지 192개의 월별 시계열자료를 이용하여 회귀분석을 하였다. 기온의 영향이 큰 에너지 수요의 특성을 반영하기 위하여 월별 더미변수를 사용하였으며, 용도별 수요특성의 반영을 위하여 용도별로 분석을 진행하였다. 분석결과 주택용, 일반용, 산업용 모든 용도에서 가스·전기 상대가격은 에너지전환효율에 각각 유의한 영향을 미치는 것으로 나와 전기요금정책이 국가 에너지효율에 영향을 미칠 것이라는 가설을 검증할 수 있었다. 즉 가스·전기 상대가격이 상승하면 에너지전환효율은 낮아질 것이라는 가설처럼 가스·전기 상대가격과 에너지전환효율은 음의 관계를 가지는 것으로 분석결과가 나왔다. 실증분석을 통하여 에너지효율은 전기요금 정책에 의해 영향을 받을 수도 있다는 것을 확인하였는데 이는 국가 에너지효율 향상을 위하여 에너지절약, 에너지기기 효율개선 등 기존의 전통적인 방법 외에 전기요금규제라는 정책수단을 통하여 에너지효율을 향상시킬 수도 있다는 의미이다. 따라서 정부는 전기요금 규제 시에 에너지 수급관리의 관점에서 에너지원간 수요대체 관계뿐만이 아니라 국가 에너지효율 향상의 관점에서 전기화 과정의 에너지 전환효율성도 고려할 필요성이 있다.Energy efficiency is a very important policy task in Korea in light of the fact that Korea relies heavily on imports for the vast majority of its energy needs. However, Korea's energy efficiency remains at the bottom of the list of the OECD (Organization for Economic Cooperation and Development) countries. Despite the government's diverse efforts to save energy and improve energy efficiency, the progress is rather slow and the energy consumption rate or Energy Intensity, which is the leading indicator of the energy efficiency, has come to a standstill or even become worse. The energy conversion loss is unavoidable in the process of using energy. When the primary energy such as coal, oil and gas is converted into the final energy or electricity, only 40% of such primary energy resources are converted into electricity, which in turn could mean that almost 95% of a total energy loss of a country derives from such electrification process. The higher the electrification, the lower the energy efficiency becomes, so to speak. The electricity demand in Korea has been rapidly growing with an average annual growth rate of approximately 4.5 percent from 2000 to 2018. Such a demand hike is due notably to convenience in use, affordable home appliances and lifestyle change. That aside, the electricity price is also one of the contributing factors to increase the power demand. The government has adopted a policy of low electricity tariff in order to stabilize the price and maintain the competitive edge of its industries. Such a low tariff policy has prompted the electricity consumption by virtue of forcing other alternative fuels switching to produce more electricity. Such status quo of fuel switching is particularly pronounced in the city gas, relative to electricity. The rise in electricity consumption coupled with the low energy conversion efficiency not only requires more fuel import from overseas to produce power but it also leads to massive infrastructure building both for the primary energy supply systems and the additional power facilities. Overall, this amounts to a nationwide loss, let alone the redundancy and inefficiency arising out of indiscriminate facility investments. As such, this study seeks to address the question "Does the relatively lower electricity price indeed aggravate the national energy efficiency? The study is also willing to verify, on an empirical basis, whether or not the correlation of the prices between electricity and gas has affected the national energy efficiency via demand substitution. For such verification, gas and electricity relative prices and energy conversion efficiency (final energy consumption/primary energy supply) were set as independent and dependent variables respectively, and a regression analysis was conducted using 192 monthly time series data from January 2003 to December 2018. Monthly dummy variables were used to reflect the characteristics of energy demand that had a significant effect on temperature, and analysis was conducted for each purpose to reflect the characteristics of demand-by-use. According to the analysis, the relative price of gas and electricity for all purposes of housing, general and industrial use has had a significant impact on energy conversion efficiency, which corroborated the hypothesis that the electricity price policy is likely to affect the national energy efficiency. In other words, just as the hypothesis that as the relative price of gas and electricity increases, the energy conversion efficiency decreases, the study shows that the relative prices of gas and electricity and energy conversion efficiency have a negative correlation. The above empirical analysis attests to a fact that the energy efficiency could be affected by the electricity price policy, which implies that it could be feasible that the energy efficiency improves through the policy measures of regulating electricity price, in addition to the existing traditional methods such as improving energy facilities efficiency and saving energy to improve the national energy efficiency. Hence, when regulating the electricity price, the government should factor into account the demand switch among different energy sources from the perspective of managing the energy supply and demand. As well as it also needs to consider the energy conversion efficiency during the electrification process in a manner to enhance the national energy efficiency.제 1 장 서론 1 제 1 절 연구의 배경 및 목적 1 제 2 절 연구의 범위 및 방법 5 제 2 장 이론적 논의 및 선행연구 6 제 1 절 이론적 논의 6 1. 공공요금 규제에 관한 이론적 논의 6 2. 에너지 수요에 관한 이론적 논의 13 3. 에너지 효율에 관한 이론적 논의 및 현황 16 제 2 절 선행연구 검토 24 1. 에너지 요금 정책에 관한 선행연구 24 2. 에너지원간 수요대체에 관한 선행연구 27 3. 에너지효율에 관한 선행연구 31 제 3 절 선행연구의 함의 및 연구의 차별성 34 제 3 장 연구 설계 37 제 1 절 연구의 분석틀 37 1. 연구모형 37 2. 연구가설 39 3. 변수설명 40 제 2 절 자료수집 및 분석방법 45 1. 자료수집 및 단위 45 2. 분석방법 48 제 3 절 자료에 대한 설명 48 1. 도시가스 가격 및 전기 가격 48 2. 에너지 전환 효율 52 제 4 장 실증분석 55 제 1 절 주택용 분석결과 55 제 2 절 일반용 분석결과 59 제 3 절 산업용 분석결과 64 제 5 장 결론 69 제 1 절 연구결과 요약 69 제 2 절 시사점 및 한계 74 참고문헌 77 Abstract 80Maste

SUMOylation of TBL1 and TBLR1 promotes androgen-independent prostate cancer cell growth.

Chronic inflammation is strongly associated with prostate cancer pathogenesis. Transducin β-like protein (TBL1) and Transducin β-like 1X-linked receptor 1 (TBLR1) have been identified recently as a coactivator for NF-κB-mediated transcription; however, the underlying mechanism by which TBL1 and TBLR1 activate NF-κB function during inflammation remains unknown. Here, we demonstrate that cytokine production is significantly elevated in androgen-independent PC-3 prostate cancer cells compared with androgen-dependent LNCaP prostate cancer cells. Elevated cytokine production positively correlates with the TBL1 and TBLR1 SUMOylation level in PC-3 cells. We show that both TBL1 and TBLR1 are SUMOylated in response to TNF-α treatment, and this increases formation of the TBL1-TBLR1-NF-κB complex, which leads to NF-κB-mediated transcriptional activation of cytokine gene expression. Conversely, SENP1-mediated deSUMOylation of TBL1 and TBLR1 inhibits NF-κB-target gene expression by dissociating TBL1 and TBLR1 from the nuclear hormone receptor corepressor (NCoR) complex. TBL1 knockdown substantially suppresses inflammatory signaling and PC-3 cell proliferation. Collectively, these results suggest that targeted SUMOylation of TBL1 and TBLR1 may be a useful strategy for therapeutic treatment of androgen-independent prostate cancer.ope

Delphinidin induces apoptosis via cleaved HDAC3-mediated p53 acetylation and oligomerization in prostate cancer cells

Delphinidin is a major anthocyanidin compound found in various fruits. It has anti-inflammatory, anti-oxidant, and various other biological activities. In this study, we identified the epigenetic modulators that mediate the apoptotic effect of delphinidin in human prostate cancer cells. We found that treatment of LNCaP cells (a p53 wild-type, human prostate cancer cell line) with delphinidin increased caspase-3, -7, and -8 activity, whereas it decreased histone deacetylase activity. Among class I HDACs, the activity of HDAC3 was specifically inhibited by delphinidin. Moreover, the induction of apoptosis by delphinidin was dependent on caspase-mediated cleavage of HDAC3, which results in the acetylation and stabilization of p53. We also observed that delphinidin potently upregulated pro-apoptotic genes that are positively regulated by p53, and downregulated various anti-apoptotic genes. Taken together, these results show that delphinidin induces p53-mediated apoptosis by suppressing HDAC activity and activating p53 acetylation in human prostate cancer LNCaP cells. Therefore, delphinidin may be useful in the prevention of prostate cancer.ope

Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5

Programmed cell death 5 (PDCD5) is believed to play a crucial role in p53 activation; however, the underlying mechanism of how PDCD5 function is regulated during apoptosis remains obscure. Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser-119, which leads to PDCD5 destabilization. Overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, efficiently suppressed CK2α-mediated stabilization of PDCD5 and p53-mediated apoptosis in response to etoposide (ET). Conversely, PPEF-1 knockdown further enhanced genotoxic stress responses. Notably, PPEF-1 suppressed p53-mediated genotoxic stress response via negative regulation of PDCD5. We also determined that overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, significantly increased tumorigenic growth and chemoresistance of A549 human lung carcinoma cells. Collectively, these data demonstrate that PPEF-1 plays a pivotal role in tumorigenesis of lung cancer cells by reducing PDCD5-mediated genotoxic stress responses.ope

Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis. [BMB Reports 2023; 56(2): 114-119].ope

Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response

The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. Here we show that programmed cell death 5 (PDCD5) selectively mediates HDAC3 dissociation from p53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Casein kinase 2 alpha phosphorylates PDCD5 at Ser-119 to enhance its stability and importin 13-mediated nuclear translocation of PDCD5. Genetic deletion of PDCD5 abrogates etoposide (ET)-induced p53 stabilization and HDAC3 cleavage, indicating an essential role of PDCD5 in p53 activation. Restoration of PDCD5(WT) in PDCD5(-/-) MEFs restores ET-induced HDAC3 cleavage. Reduction of both PDCD5 and p53, but not reduction of either protein alone, significantly enhances in vivo tumorigenicity of AGS gastric cancer cells and correlates with poor prognosis in gastric cancer patients. Our results define a mechanism for p53 activation via PDCD5-dependent HDAC3 decay under genotoxic stress conditions.ope

A study on the satisfaction of web-based health education program

Purpose: This study was to present the process of web-based educational program (WEP) development and to identify factors affecting satisfaction with WEP for the certificate of healthcare managers working at the National Health Insurance Corporation (NHIC). Methods: Subjects were healthcare managers and voluntary participants of WEP. A total of 1,449 respondents were surveyed through an online questionnaire about their satisfaction with the educational contents and system. Results: The mean contents satisfaction was 3.75 (SD 0.54), and system satisfaction 4.68 (SD 0.54). According to statistical analysis, the type of certification, experience and professional career of health care management affected contents satisfaction. And factors affecting system satisfaction were the type of certification and gender. Conclusion: WEP was utilized as a pre-requisite course for the certificate program of healthcare managers. However, the development of advanced WEP is suggested to meet the educational needs of healthcare managers who have certificate or license and their job related to healthcare managementOAIID:oai:osos.snu.ac.kr:snu2009-01/102/0000028528/4SEQ:4PERF_CD:SNU2009-01EVAL_ITEM_CD:102USER_ID:0000028528ADJUST_YN:NEMP_ID:A076124DEPT_CD:811CITE_RATE:0FILENAME:26 웹기반 건강교육 프로그램에 대한 만족도 연구.pdfDEPT_NM:간호학과EMAIL:[email protected]_YN:NCONFIRM:

Club cell-specific role of programmed cell death 5 in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF.ope