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( Ji Won Kim ),( Cheng Lin Sun ),( Sung Yoon Jeon ),( Young Hye You ),( Ju Young Shin ),( Seung Hwan Lee ),( Jae Hyoung Cho ),( Chung Gyu Park ),( Kun Ho Yoon ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.1
The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into β-cells. After transplantation of NPCCs, the ductal cyst area and β-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3β gene expression was significantly downregulated following Dx treatment, whereas PGC-1α expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into β-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1α plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final β-cell mass in grafts. [BMB reports 2012; 45(1): 51-56]
You, Eunae,Huh, Yun Hyun,Kwon, Ahreum,Kim, So Hee,Chae, In Hee,Lee, Ok-Jun,Ryu, Je-Hwang,Park, Min Ho,Kim, Ga-Eon,Lee, Ji Shin,Lee, Kun Ho,Lee, Yong-Seok,Kim, Jung-Woong,Rhee, Sangmyung,Song, Woo Keun American Association for Cancer Research 2017 Cancer Research Vol.77 No.17
<P>Disrupting expression of a determinant of microtubule acetylation may pose an effective therapeutic strategy to treat breast cancers.</P><P>Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. <I>Spin90</I> deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. <I>Spin90</I> depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. <I>Cancer Res; 77(17); 4710–22. ©2017 AACR</I>.</P>
Kim, Ji-Won,You, Young-Hye,Ham, Dong-Sik,Cho, Jae-Hyoung,Ko, Seung-Hyun,Song, Ki-Ho,Son, Ho-Young,Suh-Kim, Haeyoung,Lee, In-Kyu,Yoon, Kun-Ho Association for the Study of Internal Secretions 2009 Endocrinology Vol.150 No.9
<P>Peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) is significantly elevated in the islets of animal models of diabetes. However, the molecular mechanism has not been clarified. We investigated whether the suppression of PGC-1alpha expression protects against beta-cell dysfunction in vivo and determined the mechanism of action of PGC-1alpha in beta-cells. The studies were performed in glucolipotixicity-induced primary rat islets and INS-1 cells. In vitro and in vivo approaches using adenoviruses were used to evaluate the role of PGC-1alpha in glucolipotoxicity-associated beta-cell dysfunction. The expression of PGC-1alpha in cultured beta-cells increased gradually with glucolipotoxicity. The overexpression of PGC-1alpha also suppressed the expression of the insulin and beta-cell E-box transcription factor (BETA2/NeuroD) genes, which was reversed by PGC-1alpha small interfering RNA (siRNA). BETA2/NeuroD, p300-enhanced BETA2/NeuroD, and insulin transcriptional activities were significantly suppressed by Ad-PGC-1alpha but were rescued by Ad-siPGC-1alpha. PGC-1alpha binding at the glucocorticoid receptor site on the BETA2/NeuroD promoter increased in the presence of PGC-1alpha. Ad-siPGC-1alpha injection through the celiac arteries of 90% pancreatectomized diabetic rats improved their glucose tolerance and maintained their fasting insulin levels. The suppression of PGC-1alpha expression protects the glucolipotoxicity-induced beta-cell dysfunction in vivo and in vitro. A better understanding of the functions of molecules such as PGC-1alpha, which play key roles in intracellular fuel regulation, could herald a new era of the treatment of patients with type 2 diabetes mellitus by providing protection from glucolipotoxicity, which is an important cause of the development and progression of the disease.</P>
Kim, Ji-Won,Park, Shin-Young,You, Young-Hye,Ham, Dong-Sik,Park, Heon-Seok,Lee, Seung-Hwan,Yang, Hae Kyung,Yoon, Kun-Ho by Lippincott Williams Wilkins 2014 Transplantation Vol.97 No.3
BACKGROUND: Peroxisome proliferator-activated receptor gamma-coactivator-1α (PGC-1α) has recently been implicated as a crucial factor in the glucocorticoid-suppressed expansion and transdifferentiation of porcine neonatal pancreatic cell clusters (NPCCs). However, the molecular mechanism has not been clarified. METHODS: We investigated whether the suppression of PGC-1α expression protects against &bgr;-cell dysfunction induced by dexamethasone (Dx) treatment in vitro and in vivo and determined the mechanism of action of PGC-1α in porcine NPCCs. RESULTS: The reduction in Pdx-1 gene expression caused by either Dx treatment or PGC-1α overexpression was normalized by siPGC-1α. Nuclear FOXO1 and cytoplasmic Pdx-1 were detected after Dx treatment. However, FOXO1 was observed in the cytoplasm, and Pdx-1 was observed in the nucleus after siPGC-1α. Suppression of PGC-1α by siPGC-1α improved the Dx-induced repression of insulin secretion and insulin content. In vivo studies showed that the glucose level in the Ad-siPGC-1α-infected group was significantly lower than that in the Dx-treated group. Insulin expression in the graft tissue disappeared in the Dx-injected group. However, the siPGC-1α- and Dx-treated group showed increased insulin expression and an increase in graft mass, &bgr;-cell mass, and &bgr;-cell % in the graft. Conversely, the Dx-induced ductal cystic area was markedly reduced in the siPGC-1α- and Dx-treated group. CONCLUSIONS: Our results suggest that the transdifferentiation of porcine NPCCs into &bgr; cells is influenced by the duration of the Dx treatment, which might result from the suppression of key pancreatic transcription factors. PGC-1α is an attractive target for modulating the deleterious effects of glucocorticoids on pancreatic stem cells.
EFFECT OF PURIFIED ALGINATE MICROCAPSULES ON THE REGENERATION OF CHONDROCYTES
Hwang, Ji Hye,Kim, On You,Kim, A Ram,Bae, Ji Yeon,Jeong, Su Mi,Shim, Jung Bo,Yoon, Kun Ho,Lee, Dongwon,Khang, Gilson National Taiwan University 2012 Biomedical engineering Vol.24 No.3
<P> Adult articular cartilage tissue has poor capability of self-repair. Therefore, a variety of tissue engineering approaches are motivated by the clinical need for articular repair. Alginate has been used as a biomaterial for cartilage regeneration. The alginate is a natural polymer that is extracted from seaweeds and purification. However, the main drawback is the immune rejection in vivo. To overcome this problem, we have developed the biocompability of alginate using modified Korbutt method. After alginate was purified, purified alginate microcapsules were used in cartilage regeneration. Chondrocytes were seeded in purified and nonpurified alginate microcapsules, and then cell viability, proliferation and phenotype were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to confirm mRNA expression on collagen type I and collagen type II for chondrocytes phenotype. Hematoxylin and eosin (H&E) and Safranin-O histological staining showed tissue growth at the interface during the first 10 days. In this study, chondrocytes in purified alginate microcapsules had higher cell viability, proliferation and more phenotype expression than those in nonpurified alginate microcapsules. The results suggest that the purified alginate microcapsule is useful for cartilage regeneration. </P>
소면적 재배작물 중 살충제 Afidopyropen 및 대사체 M440I007의 잔류 특성
박소현 ( So-hyun Park ),임은지 ( Eun-ji Lim ),우상원 ( Sang-won Woo ),박주언 ( Joo-un Park ),배병진 ( Byung-jin Bae ),정혜진 ( Hye-jin Jeong ),장유진 ( You-jin Jang ),박종우 ( Jong-woo Park ),이근식 ( Kun-sik Lee ),채석 ( Seok Ch 한국환경농학회 2021 한국환경농학회 학술대회집 Vol.2021 No.-
현재 우리나라는 2019년부터 농약허용물질목록고시제(Positive List System, PLS)를 전면시행하여 잔류허용기준 미설정 농약에 대한 잔류허용기준을 0.01 mg/kg으로 일괄 적용하여 관리하고 있다. 특히, 소면적 재배작물들은 재배면적이 작고 농약 사용량이 적어 농약 회사들이 등록을 기피하고 있어 잔류허용기준이 설정된 농약의 수가 제한적이다. 이에 본 연구는 소면적 재배작물인 엇갈이배추, 시금치, 미나리, 쪽파에 진딧물류의 방제에 사용되는 살충제 Afidopyropen의 잔류성을 구명하여 농약품목등록 자료 및 잔류농약의 안전성 평가를 위한 기초자료로 활용하고자 하였다. 시험농약인 Afidopyropen 2.5% 미탁제는 최근 개발된 살충제로서 소면적 엽경채류인 엇갈이배추, 시금치, 미나리, 쪽파에 2,000배 희석으로 7일간격 2회 살포하여 잔류특성을 연구하였다. Afidopyropen 및 대사체 M440I007의 4가지 작물에 대한 정량한계는 모두 0.01 mg/kg 이었으며 회수율 시험은 LOQ, 10LOQ, 최고잔류농도 수준으로 각각 5반복으로 수행하였다. 각 작물의 회수율은 엇갈이배추 82.1∼103.8 %, 시금치 75.9∼94.2 %, 미나리 83.2∼104.7 %, 쪽파 79.9∼109.4 %로 유효한 회수율 범위를 나타내었다. Afidopyropen의 합산 잔류량은 엇갈이배추 0.01∼0.60 mg/kg, 시금치 0.01∼1.22 mg/kg, 미나리 0.01∼0.68 mg/kg, 쪽파 <0.01∼0.23 mg/kg 이었으며, 최종 약제살포 후 경과일수에 따라 경시적으로 감소하는 경향을 나타내었다. 각 작물의 MRL 설정은 엇갈이배추의 경우는 MRL이 0.5 mg/kg으로 설정이 되어 있으며, 시금치.미나리.쪽파의 경우는 현재 MRL이 미설정으로 본 잔류시험의 결과를 토대로 MRL을 0.5∼1.0mg/kg으로 추천하여 안전사용기준을 수확 7∼3일전 2회 처리로 제안하였다.