• Title/Summary/Keyword: Translational research

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HS 1-Associated Protein X-1 Is Cleaved by Caspase-3 During Apoptosis

  • Lee, Ah Young;Lee, Yoora;Park, Yun Kyung;Bae, Kwang-Hee;Cho, Sayeon;Lee, Do Hee;Park, Byoung Chul;Kang, Sunghyun;Park, Sung Goo
    • Molecules and Cells
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    • v.25 no.1
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    • pp.86-90
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    • 2008
  • Caspase-3 (CASP3) plays a key role in apoptosis. In this study, HAX-1 was identified as a new substrate of CASP3 during apoptosis. HAX-1 was cleaved by CASP3 during etoposide-(ETO) induced apoptosis, and this event was inhibited by a CASP3-specific inhibitor. The cleavage site of HAX-1, at $Asp^{127}$, was located using N-terminal amino acid sequencing of in vitro cleavage products of recombinant HAX-1. Overexpression of HAX-1 inhibited ETO-induced apoptotic cell death. It also inhibited CASP3 activity. Together, these results suggest that HAX-1, a substrate of CASP3, inhibits the apoptotic process by inhibiting CASP3 activity.

A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Interactome Analysis of Yeast Glutathione Peroxidase 3

  • Lee, Phil-Young;Bae, Kwang-Hee;Kho, Chang-Won;Kang, Sung-Hyun;Lee, Do-Hee;Cho, Sa-Yeon;Kang, Seong-Man;Lee, Sang-Chul;Park, Byoung-Chul;Park, Sung-Goo
    • Journal of Microbiology and Biotechnology
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    • v.18 no.8
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    • pp.1364-1367
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    • 2008
  • Oxidative stress damages all cellular constituents, and therefore, cell has to possess various defense mechanisms to cope. Saccharomyces cerevisiae, widely used as a model organism for studying cellular responses to oxidative stress, contains three glutathione peroxidase (Gpx) proteins. Among them, Gpx3 plays a major defense role against oxidative stress in S. cerevisiae. In this study, in order to identity the new interaction proteins of Gpx3, we carried out two-dimensional gel electrophoresis after immunoprecipitation (IP-2DE), and MALDI-TOF mass spectrometry. The results showed that several proteins including protein disulfide isomerase, glutaredoxin 2, and SSY protein 3 specifically interact with Gpx3. These findings led us to suggest the possibility that Gpx3, known as a redox sensor and ROS scavenger, has another functional role by interacting with several proteins with various cellular functions.

Monoclonal antibody K312-based depletion of pluripotent cells from differentiated stem cell progeny prevents teratoma formation

  • Park, Jongjin;Lee, Dong Gwang;Lee, Na Geum;Kwon, Min-Gi;Son, Yeon Sung;Son, Mi-Young;Bae, Kwang-Hee;Lee, Jangwook;Park, Jong-Gil;Lee, Nam-Kyung;Min, Jeong-Ki
    • BMB Reports
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    • v.55 no.3
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    • pp.142-147
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    • 2022
  • Human pluripotent stem cells (PSCs) have been utilized as a promising source in regenerative medicine. However, the risk of teratoma formation that comes with residual undifferentiated PSCs in differentiated cell populations is most concerning in the clinical use of PSC derivatives. Here, we report that a monoclonal antibody (mAb) targeting PSCs could distinguish undifferentiated PSCs, with potential teratoma-forming activity, from differentiated PSC progeny. A panel of hybridomas generated from mouse immunization with H9 human embryonic stem cells (hESCs) was screened for ESC-specific binding using flow cytometry. A novel mAb, K312, was selected considering its high stem cell-binding activity, and this mAb could bind to several human induced pluripotent stem cells and PSC lines. Cell-binding activity of K312 was markedly decreased as hESCs were differentiated into embryoid bodies or by retinoic acid treatment. In addition, a cell population negatively isolated from undifferentiated or differentiated H9 hESCs via K312 targeting showed a significantly reduced expression of pluripotency markers, including Oct4 and Nanog. Furthermore, K312-based depletion of pluripotent cells from differentiated PSC progeny completely prevented teratoma formation. Therefore, our findings suggest that K312 is utilizable in improving stem cell transplantation safety by specifically distinguishing residual undifferentiated PSCs.

Current situation of Translational research on Acupuncture, Moxibustion and Pharmacopuncture (침구와 약침에 대한 중개연구 현황)

  • Sin, Dae Chul;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.33 no.2
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    • pp.109-116
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    • 2016
  • Objectives : Our primary objective lies in understanding the current landscape of translational research on acupuncture, moxibustion and pharmacopuncture. Methods : We searched our own selection of keywords of acupuncture, moxibustion and pharmacopuncture and translational research from three overseas databases (Pubmed, Scopus, Medicine) and four domestic databases (DBpia, KISS, Riss4u, Korea Med). Results : We have chosen 41 articles in total-40 articles on acupunture, 6 article on moxibustion(5 articles were duplicated in use in each category). Origin-wise, 48.8 %/24.8 %/17.0 % of our articles pool came from USA/China/Korea, respectively. UK, Austria, Thailand and Italy contributed the rest of our article pool. For those articles written in USA and China, review articles were the most common type. For the US articles, all 10 review articles were non-systematic reviews, while, for China's contribution, one out of 4 review articles were systematic review. Type-wise, our research pool's breakdown is as follows ; 17 review articles, 11 experimental research, 2 randomized controlled trials(RCT), 1 clinical trial, 4 conference reports, 1 letter, 1 study protocol and 4 uncategorized. Topic-wise, brain-neurology was most frequently referred with 8 articles, followed by parkinson's disease (3 articles) and epilepsy (2 articles). Conclusion : 1. In terms of research submission articles, Korea appears to be lacking translational research on acupuncture, moxibustion and pharmacopuncture, compared to USA and China, in our view. 2. Unlike the cases of USA and China, most of Korean translational research is limited to doing a T1 level of translational research. In order to bring bench-to-bedside to light. we believe, there should be more studies, and thereby a certain level of activation, to the T2 level of translational research in Korea. 3. Further, in our view there should be more efforts to improve article quality at the T1 level of translational research, which eventually becomes the fundamentals of the next level of research (i.e. T2 research), as well as to increase the number of research submissions, going forward.

Phosphoproteomic Analysis of AML14.3D10 Cell Line as a Model System of Eosinophilia

  • Ryu, Su-In;Kim, Won-Kon;Cho, Hyun-Ju;Lee, Phil-Young;Jung, Hye-Yun;Yoon, Tae-Sung;Moon, Jeong-Hee;Kang, Sung-Hyun;Poo, Ha-Ryoung;Bae, Kwang-Hee;Lee, Sang-Chul
    • BMB Reports
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    • v.40 no.5
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    • pp.765-772
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    • 2007
  • Eosinophils act as effectors in the inflammatory reactions of allergic diseases including atopic dermatitis. Atopic dermatitis patients and others with allergic disorders suffer from eosinophilia, an accumulation of eosinophils due to increased survival or decreased apoptosis of eosinophils. In this study, a differential phosphoproteome analysis of AML14.3D10 eosinophil cell line after treatment with IL-5 or dexamethasone was conducted in an effort to identify the phosphoproteins involved in the proliferation or apoptosis of eosinophils. Proteins were separated by 2-DE and alterations in phosphoproteins were then detected by Pro-Q Diamond staining. The significant quantitative changes were shown in nineteen phosphoproteins including retinoblastoma binding protein 7, MTHSP75, and lymphocyte cytosolic protein 1. In addition, seven phosphoproteins including galactokinase I, and proapolipoprotein, were appeared after treatment with IL-5 or dexamethasone. Especially, the phospho-APOE protein was down-regulated in IL-5 treated AML14.3D10, while the more heavily phosphorylated APOE form was induced after dexamethasone treatment. These phosphoproteome data for the AML14.3D10 cell line may provide clues to understand the mechanism of eosinophilia as well as allergic disorders including atopic dermatitis.

Comparative proteomic analysis of peripheral blood mononuclear cells from atopic dermatitis patients and healthy donors

  • Kim, Won-Kon;Cho, Hyun-Ju;Ryu, Su-In;Hwang, Hyang-Ran;Kim, Do-Hyung;Ryu, Hye-Young;Chung, Jin-Woong;Kim, Tae-Yoon;Park, Byoung-Chul;Bae, Kwang-Hee;Ko, Yong;Lee, Sang-Chul
    • BMB Reports
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    • v.41 no.8
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    • pp.597-603
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    • 2008
  • Atopic dermatitis (AD) is a chronic inflammatory skin disease that induces changes in various inflammatory skin cells. The prevalence of AD is as high as 18% in some regions of the world, and is steadily rising. However, the pathophysiology of AD is poorly understood. To identify the proteins involved in AD pathogenesis, a comparative proteomic analysis of protein expression in peripheral blood mononuclear cells isolated from AD patients and healthy donors was conducted. Significant changes were observed in the expressions of fourteen proteins, including the vinculin, PITPNB, and Filamin A proteins. Among the proteins, $\alpha$-SNAP and FLNA decreased significantly, and PITPNB increased significantly in AD patients compared with control subjects; these findings were further confirmed by real-time PCR and Western blot analysis. The comparative proteome data may provide a valuable clue to further understand AD pathogenesis, and several differentially regulated proteins may be used as biomarkers for diagnosis and as target proteins for the development of novel drugs.

Application of Near-Infrared Fluorescence Imaging with Indocyanine Green in Totally Laparoscopic Distal Gastrectomy

  • Liu, Maoxing;Xing, Jiadi;Xu, Kai;Yuan, Peng;Cui, Ming;Zhang, Chenghai;Yang, Hong;Yao, Zhendan;Zhang, Nan;Tan, Fei;Su, Xiangqian
    • Journal of Gastric Cancer
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    • v.20 no.3
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    • pp.290-299
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    • 2020
  • Purpose: Recently, totally laparoscopic gastrectomy has been gradually accepted by surgeons worldwide for gastric cancer treatment. Complete dissection of the lymph nodes and the establishment of the surgical margin are the most important considerations for curative gastric cancer surgery. Previous studies have demonstrated that indocyanine green (ICG)-traced laparoscopic gastrectomy significantly improves the completeness of lymph node dissection. However, it remains difficult to identify the tumor location intraoperatively for gastric cancers that are staged ≤T3. Here, we investigated the feasibility of ICG fluorescence for lymph node mapping and tumor localization during totally laparoscopic distal gastrectomy. Materials and Methods: Preoperative and perioperative data from consecutive patients with gastric cancer who underwent a totally laparoscopic distal gastrectomy were collected and analyzed. The patients were categorized into the ICG (n=61) or the non-ICG (n=75) group based on whether preoperative endoscopic mucosal ICG injection was performed. Results: The ICG group had a shorter operation time and less intraoperative blood loss. Moreover, significantly more lymph nodes were harvested in the ICG group than the non-ICG group. No pathologically positive margin was found and there was no significant difference in either the proximal or distal surgical margins between the 2 groups. Conclusions: Near-infrared fluorescence imaging with ICG can be successfully used in totally laparoscopic distal gastrectomy, and it contributes to both the completeness of D2 lymph node dissection and confirmation of the gastric transection line. Well-designed prospective randomized studies are needed in the future to fully validate our findings.

First detection of a G1-like H9N2 virus in Russia, 2018

  • Sharshov, Kirill;Kurskaya, Olga;Sobolev, Ivan;Leonov, Sergey;Kabilov, Marsel;Tatyana, Alikina;Alekseev, Alexander;Derko, Anastasiya;Yushkov, Yuriy;Saito, Takehiko;Uchida, Yuko;Mine, Junki;Irza, Victor;Shestopalov, Alexander
    • Korean Journal of Veterinary Research
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    • v.59 no.1
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    • pp.37-42
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    • 2019
  • Worldwide, avian influenza H9N2 viruses of different lineages are the most widespread viruses in poultry. However, to date, cases in Russia have not been documented. In this study, we report the first detection of a G1-like H9N2 virus from poultry sampled at live-bird markets in Russia (Far East region) during the winter of 2018 (isolate A/chicken/Amur_Russia/17/2018). We assume there has been further circulation of the A/chicken/Amur_Russia/17/2018 H9N2 virus in the Russian Far East with possible distribution to other regions or countries in 2018-2019.