• 대한생식의학회:학술대회논문집
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• 대한불임학회 2006년도 The 5th Biannual Meeting of Pacific Rim Society for Fertility and Sterility
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• pp.160.1-160.1
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• 2006

• 한국발생생물학회지:발생과생식
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• 제23권4호
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• pp.391-399
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• 2019

Nicotinamide is used to maturate pancreatic progenitors from embryonic stem cells (ESCs) into insulin-producing cells (IPCs). It has been known that nicotinamide inhibits the enzymatic activity of SIRT1, an NAD⁺-dependent deacetylase. Here we show that SIRT1 knockdown enhances the differentiation of human ESCs into IPCs. SIRT1 knockdown enhances the clustering size of IPCs and the expression of pancreatic genes including c-peptide, pancreas/duodenum homeobox protein 1 (PDX1), insulin, somatostatin, glucagon and Nkx6.1 in human ESC-derived IPCs. In addition, We found that IPCs differentiated from SIRT1 knockdowned human ESCs have more zinc compared to those from control human ESCs. Our data suggest that SIRT1 negatively regulates the differentiation of β cells from human ESCs.

• BMB Reports
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• 제51권5호
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2004년도 제47차 추계학술대회
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• pp.40-41
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• 2004

• Journal of applied mathematics & informatics
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• 제35권1_2호
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• pp.121-130
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• 2017

This study is concerned with the existence of positive solution for the following nonlinear elliptic system $$\{-M_1(\int_{\Omega}{\mid}x{\mid}^{-ap}{\mid}{\nabla}u{\mid}^pdx)div({\mid}x{\mid}^{-ap}{\mid}{\nabla}u{\mid}^{p-2}{\nabla}u)\\{\hfill{120}}={\mid}x{\mid}^{-(a+1)p+c_1}\({\alpha}_1A_1(x)f(v)+{\beta}_1B_1(x)h(u)\),\;x{\in}{\Omega},\\-M_2(\int_{\Omega}{\mid}x{\mid}^{-bq}{\mid}{\nabla}v{\mid}^qdx)div({\mid}x{\mid}^{-bq}{\mid}{\nabla}v{\mid}^{q-2}{\nabla}v)\\{\hfill{120}}={\mid}x{\mid}^{-(b+1)q+c_2}\({\alpha}_2A_2(x)g(u)+{\beta}_2B_2(x)k(v)\),\;x{\in}{\Omega},\\{u=v=0,\;x{\in}{\partial}{\Omega},$$ where ${\Omega}$ is a bounded smooth domain of ${\mathbb{R}}^N$ with $0{\in}{\Omega}$, 1 < p, q < N, $0{\leq}a$ < $\frac{N-p}{p}$, $0{\leq}b$ < $\frac{N-q}{q}$ and ${\alpha}_i,{\beta}_i,c_i$ are positive parameters. Here $M_i,A_i,B_i,f,g,h,k$ are continuous functions and we discuss the existence of positive solution when they satisfy certain additional conditions. Our approach is based on the sub and super solutions method.

• BMB Reports
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• 제42권10호
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• pp.661-666
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• 2009

Porcine pancreas development is not well studied at the molecular level despite being a therapeutic resource for diabetic patients. In this study, we investigated expression of lineage markers and performed proteomic analysis. Expression of the early lineage markers Pdx1 and Ptf1a was developmentally conserved between mice and pigs, whereas expression of the islet differentiation marker Pax4 was delayed in porcine compared with murine pancreas development. Proteomic analysis found that expression levels of chymotrypsinogen were down-regulated during porcine pancreas development while those of digestive enzymes like lipases, elastase and serine protease were up-regulated. In addition, specific isoforms of protein folding assistants such as protein disulfide isomerase and prefoldin were expressed at specific stages during the maturation of digestive enzymes. Taken together, these results show that development of the porcine pancreas is regulated by a concerted interplay of pancreas lineage marker proteins and other specified proteins, resulting in a functional endocrine and exocrine organ.

• Genomics & Informatics
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• 제12권4호
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• pp.236-239
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• 2014

The genetic regulation of glucose and insulin levels might be modified by adiposity. With regard to the genetic factors that are altered by adiposity, a large meta-analysis on the interactions between genetic variants and body mass index with regard to fasting glucose and insulin levels was reported by the Meta-Analyses of Glucose- and Insulin-related trait Consortium (MAGIC), based on European ancestry. Because no replication study has been performed in other ethnic groups, we first examined the link between reported single-nucleotide polymorphisms (SNPs) and fasting glucose and insulin levels in a large Korean cohort (Korean Genome and Epidemiology Study cohort [KoGES], n = 5,814). The MAGIC study reported 7 novel SNPs for fasting glucose levels and 6 novel SNPs for fasting insulin levels. In this study, we attempted to replicate the association of 5 SNPs with fasting glucose levels and 5 SNPs with fasting insulin levels. One SNP (rs2293941) in PDX1 was identified as a significant obesity-modifiable factor in Koreans. Our results indicate that the novel loci that were identified by MAGIC are poorly replicated in other ethnic groups, although we do not know why.

• Genomics & Informatics
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• 제20권3호
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• pp.26.1-26.19
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• 2022

Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

• BMB Reports
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• 제45권1호
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• pp.51-56
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• 2012

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 ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ 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 ${\beta}$-cell mass in grafts.

• 한국식품과학회지
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• 제45권4호
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• pp.488-494
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• 2013

제2형 당뇨질환모델인 KK-$A^y$를 이용하여 녹차와 발효녹차의 항당뇨 활성을 측정한 결과, 발효 녹차는 비발효녹차에 비해 높은 항당뇨 활성이 있는 것으로 분석되었다. 발효녹차 섭취군의 혈당은 당뇨 대조군보다 낮게 유지되었으며, 60일 이후에는 시판 건강기능식품 섭취군(양성대조군)과 유사한 수준으로 유지되었을 뿐만 아니라 당화혈색소값도 8.08%로 대조군 및 양성대조군 군보다 낮게 나타났다. 간 조직의 DNA microarray 분석결과, 이러한 발효녹차의 항당뇨 활성은 glycolysis 활성화를 통한 glucose 이용율 및 베타세포 function 증가에 의한 것으로 사료된다. 또한 발효녹차는 혈중 triglyceride 수치를 낮추고 HDL-cholesterol 수치를 높이는 등 당뇨로 인해 발생할 수 있는 지질대사이상 개선에도 효과가 있음을 알 수 있었다. 이로 미루어 보아 발효녹차는 항당뇨 관련 건강기능식품으로의 상업적 이용가능성이 높을 것으로 생각된다.