http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma
Yoo, Hae Yong,Sung, Min Kyung,Lee, Seung Ho,Kim, Sangok,Lee, Haeseung,Park, Seongjin,Kim, Sang Cheol,Lee, Byungwook,Rho, Kyoohyoung,Lee, Jong-Eun,Cho, Kwang-Hwi,Kim, Wankyu,Ju, Hyunjung,Kim, Jaesang,K Nature Publishing Group, a division of Macmillan P 2014 Nature genetics Vol.46 No.4
The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples showed that the mutation was specific to T cell lymphoma and was absent from B cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature using multiple molecular assays. Molecular modeling and docking simulations provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val mutant. Our experimental data and modeling results suggest that the RHOA mutation encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and through integrated pathway analysis, we build a comprehensive signaling network for AITL oncogenesis.
Ju Hee Oh,Dae Won Jun,Hye Young Kim,Seung Min Lee,Eileen L. Yoon,Jungwook Hwang,Jung Hwan Park,Hanbi Lee,Wankyu Kim,Hyunsung Kim 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3
Background/Aims: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). Methods: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. Results: DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. Conclusions: The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.
Severe Asthma May Be Associated with the Adverse COVID-19 Outcome
( Jae Seok Jeong ),( Yong Chul Lee ),( Jin Young Choi ),( Seong Kug Eo ),( Yeo-gha Yoon ),( Wankyu Kim ),( Jong Seung Kim ),( Hae Jin Park ),( Kyung Hwa Park ),( So Ri Kim ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-
Asthma, a major respiratory illness affecting over 300 million people worldwide, is not regarded as a major co-morbid condition in COVID-19 pandemic, rather, allergic endotype has been suggested to be protective for viral contraction. However, given the heterogeneity of asthma, there is uncertainty on the impact of respiratory SARS-CoV-2 infection on each asthma subtype. Fungal sensitization has been reported as one of risk factors for developing severe asthma and, previously, we demonstrated the corticosteroid-resistant endotype of fungal allergic asthma experimentally induced by Aspergillus fumigatus (Af ) extracts, wherein NLRP3 inflammasome assembly/activation in airway epithelium plays a key role. Herein, to investigate the effects of respiratory SARS-CoV-2 infection in severe asthma, we designed a murine model that mimics the development of COVID-19 in severe fungal allergic lung inflammation using SARS-CoV-2-susceptible hACE2 transgenic mice. We also performed transcriptome analysis of lung tissues and compared the expression profiles with those from COVID-19 public datasets. Firstly, to assess clinically the impact of co-morbid severe asthma on COVID-19 outcome, we analyzed the nationwide data of patients who underwent SARS-CoV-2 testing. Notably, mortality rate of COVID-19 was increased in severe asthmatics who were dependent on corticosteroids. In Af-induced experimental system, we observed that SARS-CoV-2- induced lung inflammation coincides with the deterioration of allergic airway inflammation through analyses of infiltrated airway inflammatory cells and histopathology. This phenomenon was further verified by immunoassays of inflammatory mediators well-known to mediate asthmatic (IL-5, IL-13, IL-33, and CCL11) or COVID-19-related inflammation (TNF-α, IL-6, IFN-γ, and KC). Interestingly, NLRP3 inflammasome activation was evident in the lungs including airway epithelium. Pathways related to NLRP3 inflammasome were up-regulated in gene expression profiles of Af-exposed mice and were consistent with public datasets of COVID-19 patients. Taken together, respiratory SARS-CoV-2 infection in patients with severe asthma may predispose asthma to aggravate and maybe associated with adverse COVID-19-related outcome.
김병일(Kim Byoungil),유완규(Yoo Wankyu),양미림(Yang Mirim),박용석(Park Yongseok) 대한토목학회 2012 대한토목학회논문집 C Vol.32 No.1
선반식 옹벽에서 선반은 옹벽에 작용하는 전체 수평토압의 크기를 줄여주며, 이로 인해 구조물의 전체적인 안정성이 향상된다. 이 연구에서는 아직 국내에서는 연구가 진행된 바 없는 선반식 옹벽에 작용하는 토압분포를 파악하고 캔틸레버식 옹벽에 작용하는 토압분포와 비교하기 위하여 모형시험을 실시하였다. 또한 흙 종류와 옹벽 배면의 굴착각도를 달리하여, 흙 종류와 되메움 조건이 캔틸레버식 옹벽과 선반식 옹벽에 작용하는 토압의 변화에 미치는 영향을 파악하였다. 모형시험결과 선반의 설치로 인하여 발생하는 선반식 옹벽의 토압감소는 캔틸레버식 옹벽과 비교할 경우에 뚜렷하게 발생하였고, 옹벽에 발생하는 수평변위도 선반식 옹벽이 캔틸레버식 옹벽에 비해서 작게 발생하는 것으로 나타났다. 또한 캔틸레버식 옹벽에 비해서 선반식 옹벽의 전도파괴에 대한 안정성이 상대적으로 높은 것으로 나타났다. The relieving platform has the advantage of decreasing the total lateral earth pressure on the retaining wall and increasing the overall stability of the structure. Several modeling tests were performed to determine the earth pressure distribution on the retaining wall with a relieving platform and to compare it with that of the cantilever retaining wall. Different types of soil and angle of cutting surface were used to determine the effect of the soil characteristics and the backfill conditions on these earth pressure distributions. From the modeling tests, comparisons between the retaining wall with a relieving platform and the cantilever retaining wall show that the reduction of the lateral earth pressure and deformation of wall was indicated clearly on the retaining wall with a relieving platform. And the overall stability was increased by the relieving platform.
In silico drug repositioning: from large-scale transcriptome data to therapeutics
권옥선,Wankyu Kim,Hyuk-Jin Cha,Haeseung Lee 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.10
Drug repositioning is an attractive alternative toconventional drug development when new beneficialeffects of old drugs are clinically validated because pharmacokineticand safety profiles are generally alreadyavailable. Since * 30% of drugs newly approved by theUS food and drug administration (FDA) are developedthrough drug repositioning, identifying novel usage forexisting drugs is an emerging strategy for developing diseasetreatments. With advances in next-generationsequencing technologies, available transcriptome datarelated to diseases have expanded rapidly. Harnessing theseresources enables a better understanding of disease mechanismsand drug mode of action (MOA), and moves towardpersonalized pharmacotherapy. In this review, we brieflyoutline publicly available large-scale transcriptome databasesand tools for drug repositioning. We also highlightrecent approaches leading to the discovery of novel drugtargets, drug response biomarkers, drug indications, anddrug MOA.