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RISS 인기검색어
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- 저자 : Jiyou Han (검색결과 30 건)
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Han, Jiyou,Park, Mira,Kim, Jae-Hong,Kim, Ahyoung,Won, Miae,Lee, Dong Ryul,Ko, Jeong-Jae,Yoon, Ho,Sim, Se-Hoon,Lee, Kangseok,Bae, Jeehyeon John Wiley Sons, Ltd. 2009 JOURNAL OF APPLIED TOXICOLOGY Vol.29 No.5
<P>Methiocarb is a widely used carbamate pesticide and a suspected endocrine disrupter. The objective of this study was to examine the in vivo effects of methiocarb at low doses on testicular expression of steroid receptors, spermatogenesis and sperm quality in adult mice. Eighteen-week-old DBA/2 males were treated with daily intraperitoneal injection of methiocarb (0, 0.03, 0.3, 1.0 or 3.0 µg kg<SUP>−1</SUP> of body weight) for 20 days. Kidney and liver weights were significantly increased in the 1.0 or 3.0 µg kg<SUP>−1</SUP> treatment groups (P < 0.05). The testicular expression of estrogen receptor α (ERα) was significantly increased in mice treated with methiocarb as confirmed by Western blot analysis. The sperm production and sperm quality of the methiocarb-exposed mice were not significantly altered as determined using a computer-assisted sperm analysis system. Therefore, these results demonstrate, that although the exposure to methiocarb at low doses alters testicular ERα expression in adult mice, both sperm production and quality remain unaffected. Copyright © 2009 John Wiley & Sons, Ltd.</P>
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Effects of estrogenic compounds on human embryonic stem cell differentiation
Jiyou Han,Yu Jin Jang,Su Yeon An,Jeong Sang Son,Jonghyun Kim,Jong-Hoon Kim 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-
Estrogens are ubiquitous signaling molecules that influence nearly every cell type, and exert profound effects on embryonic development, and differentiation. Wnt pathway, which recruits β-catenin into nuclei, and activates The Wnt-dependent transcription factors, also plays an important role in embryonic development and stem cell maintenance, and differentiation. Accumulating evidences indicate that potential convergence between these two pathways in carcinoma cells. However, physiological roles of estrogens in development and differentiation of human embryonic stem cells (hESCs) are relatively unknown. Here, we demonstrated that estrogenic compounds 17α-ethinylestradiol (EE2) and genistein (GEN) significantly increased β-catenin expression in undifferentiated hESCs cultured in feeder-free media. Interestingly, GEN treatement induced an increased trend of mesendodermal gene expressions, and significantly inhibited ectodermal gene expressions (Nestin and Pax6) in embrioid body (EB). Expectantly, GEN increased epithelial-mesenchymal transition (EMT) related gene expression (Snail2, and Twist), whereas decreased E-cadherin on day 6 of EB development. Taken together, these suggest that estrogens may in part the powerful effects on normal hESC differentiation. Mechanistic studies of estrogen signaling continue to suggest novel drug targets for stem cells and will also improve screening methods of developmental toxicity.
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Jiyou Han,Su Yoen An,Jong Hyun Kim,Yu Jin Jang,Jeong Sang Son,Jae Hoon Lee,Gyunggyu Lee,Ji Young Park,Jong-Hoon Kim 한국발생생물학회 2013 한국발생생물학회 학술발표대회 Vol.2013 No.8
MFG-E8 (Milk fat globule-epidermal growth factor VIII), also called lactadherin or BA46, SED1 is a glycoprotein found in milk and mammary epithelial cells, it is a major protein component associated with milk fat globule membrane. Previously, our study showed that expression of MFG-E8 is gradually increased with hepatic differentiation of human embryonic stem cells (hESCs). Therefore, we hypothesized that MFG-E8 would be an early cancer stem cell marker, which may predict cancer progression. Our results showed that MFG-E8 was expressed in various human cancer cell lines such as HepG2, Hep3B, and Huh7. Production and secretion of the MFG-E8 were also confirmed in the conditioned media of those three cell lines using enzyme-linked immunosorbent assay. Next, we analyzed the MFG-E8 expression in 11 clinical cases of cholangiocellular carcinoma (CC) and 33 cases of hepatocellular carcinoma (HCC) by immunohistochemistry and examined the potential correlation with β-catenin and AFP, which are known cancer markers. According to hitological criteria, the progression of HCC and CC was evaluated and classified into high, low, metastatic, and well-, moderate-, poor-differentiated, respectively. Statistical analysis indicated that incidence of both HCC and CC is significantly associated with male compared to female (P<0.05). Tumor size also has positive correlation with age (r2=08948). Our immunohistochemistry data showed that MFG-E8 was expressed both HCC and CC tissue. Interestingly, the MFG-E8 expression was significantly increased with cancer progression (P<0.05) in both cases. Additionally, b-cateninexpression was increased and its localization was changed from membrane to cytoplasm and nucleus with the degree of HCC. Likely b-catenin, AFP was also increased with the degree of HCC but it was not correlated with severalty of CC. Importantly, both AFP and b-catenin were highly co-localized with MFG-E8 in HCC. These results suggest that MFG-E8 may have important physiological roles and its expression in HCC and CC would be considered as an important prognostic factor.
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Park, Ji Young,Han, Jiyou,Jung, Hyo Sung,Lee, Gyunggyu,Kim, Hyo Jin,Cho, Gun-Sik,Park, Han-Jin,Han, Choongseong,Kim, Jong Seung,Kim, Jong-Hoon Elsevier 2019 Biomaterials Vol.222 No.-
<P><B>Abstract</B></P> <P>Hepatocytes derived from human pluripotent stem cells (hPSCs) are promising candidates for cell therapy and drug discovery. However, it remains challenging to efficiently purify hepatocytes from undesired cell types after differentiation and to accurately monitor grafted cells after transplantation. Indocyanine Green (ICG), an FDA-approved, near-infrared (NIR) dye, has been used for various clinical purposes and is exclusively taken up by hepatocytes. However, ICG has a long emission wavelength (λ<SUB>em</SUB> > 800 nm) that is beyond the detection range of fluorescence-activated cell sorting (FACS) systems. Moreover, it is easily eliminated from hepatocytes, hindering its application for NIR imaging. Here, we designed and synthesized two different probes based on the properties of ICG; 1) hepatocyte purifying agent (<B>HPA,</B> λ<SUB>em</SUB> = 562 nm) for <I>in vitro</I> sorting and 2) hepatocyte imaging agent (<B>HIA,</B> λ<SUB>em</SUB> = 817 nm) for efficient <I>in vivo</I> NIR imaging. We obtained highly enriched populations of hPSC-derived hepatocytes (hPSC-Heps) from various hPSC lines using HPA probe-based FACS purification. In addition, HIA labelling and NIR imaging allowed the direct visualization and tracking of grafted hPSC-Heps in animals with liver injuries. These results demonstrated that these two probes could be used as powerful tools with hPSC-Heps in both cell replacement therapy and drug screening.</P>
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Perinatal exposure of fenarimol at low doses disturb reproductive performance in mice
Mira Park,Jiyou Han,Ahyoung Kim,Kangseok Lee,Jeehyeon Bae 한국발생생물학회 2010 한국발생생물학회 학술발표대회 Vol.29 No.-
Although fenarimol is a widely used chlorinated fungicide applied to fruits and vegetables and considered as a suspected endocrine disrupter (ED), transgeneration studies of fenarimol at its low doses are not available. Objectives: The aims of this study are to address the effect of perinatal exposure to low doses of fenarimol on reproductive performance and to investigate molecular and cellular mechanisms which are associated with. Methods: The body and organ weights and anogenital distance (AGD) of mice offspring (F1) maternally exposed to fenarimol were determined, and their reproductive performances were assessed by mating and ovarian follicular and sperm analyses. In addition, differentially expressed genes (DEGs) in F1 ovaries were identified by DNA microarray. Up-regulated genes were confirmed by quantitative real-time PCR (qRT-PCR) and immunohistochemical analysis. Results: Fenarimol-exposed F1 mice showed the shortened AGD, increased body weight with altered organ weights, increased number of pub, abundant follicles, and enhanced sperm count and quality. Microarray data showed 82 up-regulated and 742 down-regulated genes on the ovaries of fenarimol-exposed mice, in which Cyp17a1 and Cyp19a1 were up-regulated. Conclusions: Low doses of perinatal fenarimol exposure caused reproductive dysfunction in mice and thus can possibly impose risks on reproductive activities of human and wild-life.
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Kumar, Rajesh,Han, Jiyou,Lim, Hee-Joung,Ren, Wen Xiu,Lim, Ja-Yun,Kim, Jong-Hoon,Kim, Jong Seung American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.51
<P>Activation of apoptosis, the cell death machinery, in tumor cells by organelle-specific delivery of antitumor theranostic agent is the utmost challenge in cancer therapy. Herein, we developed a highly efficient mitochondria-targeting antitumor theranostic prodrug <B>7</B> that contained two molecules of drug 5′-deoxy-5-fluorouridine and an apoptotic marker ethidium for self-monitoring intrinsic (mitochondrial) apoptosis after its activation in tumor cells. Theranostic <B>7</B> was activated by endogenously produced mitochondrial-overexpressed H<SUB>2</SUB>O<SUB>2</SUB> and released drug 5′-deoxy-5-fluorouridine and apoptotic marker ethidium to the tumor cells. The <I>in vitro</I> and <I>in vivo </I>drug release was monitored by observing the fluorescence changes of ethidium. Theranostic <B>7</B> exhibited an enhanced cytotoxicity over commercial 5-fluorouracil (an active drug of 5′-deoxy-5-fluorouridine) leading to intrinsic apoptosis monitored by in situ generated ethidium. Enhanced expression of mitochondria-mediated apoptotic genes (NOXA, PUMA, BID, BAX, and BAK), Cyt C, Caspase-3 and -9, and cell surface death receptors was observed after theranostic 7 activation in tumor cells. <I>In vivo</I> and <I>ex vivo</I> xenografts revealed that theranostic <B>7</B> significantly inhibited tumor progression and cured the tumor-bearing mice. Such organelle-specific theranostic strategies have great potential for the early diagnosis and precise treatment of cancer.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-51/ja510421q/production/images/medium/ja-2014-10421q_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja510421q'>ACS Electronic Supporting Info</A></P>
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Ji Young Park,Jiyou Han,Soo Jin Uhm,Jong Hyun Kim,Jeong Sang Son,Yu Jin Jang,Jae Hun Lee,Gyunggyu Lee,Jong Hoon Kim,Jong Seung Kim 한국발생생물학회 2015 한국발생생물학회 학술발표대회 Vol.2015 No.9
Hepatocytes and hepatic progenitors derived from human ES cells may be a useful source for clinical application. Therefore, identification and purification of these cell types would be following important issues. There are very few candidate surface markers that can be used to identify and purify hepatic progenitor cells. In addition, indocyanine-green can be uptaken by mature hepatocytes, but cannot be applied for fluorescence activated cell sorting (FACS) due to its long emission wavelength. In the present study, we tested EpCAM as a potential marker for magnetic-activated cell sorting (MACS) of hepatic progenitors and also modified indocyanine-green into fluorescent indomonocarbocyanine for FACS-mediated sorting of mature hepatocytes after differentiation of human ES cells. Hepatic progenitor cells were sorted by MACS after incubation with anti-human EpCAM antibodies. After the final differentiation, the differentiated cells and mouse primary hepatocytes (control group) were incubated with indomonocarbocyanine and were sorted by FACS. MACS and immunocytochemistry data showed that approximately 45% of differentiated cells were EpCAM-positive cells. EpCAM-positive cells expressed α-fetoprotein, FOXa2, HnF4a, and CK18. Differentiation efficiency into albumin-positive cells was significantly higher in EpCAM-positive cells, compared to EpCAM-negative cells. Importantly, indomonocarbocyanine successfully stained cells that expressed ALB. Furthermore, FACS analysis data showed that the purity of hepatocytes that expressed albumin was significantly increased after purification of indomonocarbocyanine-positive cells. Our data demonstrated that human ES cell-derived hepatic progenitors can be efficiently isolated by MACS using EpCAM antibody. In addition, we also showed that indomonocarbocyanine can be successfully used to identify and purify mature hepatocytes using FACS.
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