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      • KCI등재

        Chrysophanol-induced Necrotic-like Cell Death through an Impaired Mitochondrial ATP Synthesis in Hep3B Human Liver Cancer Cells

        Chien-Hang Ni,Jing-Gung Chung,Po-Yuan Chen,Hsu-Feng Lu,Jai-Sing Yang,Hui-Ying Huang,Shin-Hwar Wu,Siu-Wan Ip,Chin-Tung Wu,Su-Yin Chiang,Jaung-Geng Lin,W. Gibson Wood 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

        Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.

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      • KCI등재후보

        The development of Taiwan Fracture Liaison Service network

        Lo-Yu Chang,Keh-Sung Tsai,Jen-Kuei Peng,Chung-Hwan Chen,Gau-Tyan Lin,Chin-Hsueh Lin,Shih-Te Tu,I-Chieh Mao,Yih-Lan Gau,Hsusan-Chih Liu,Chi-Chien Niu,Min-Hong Hsieh,Jui-Teng Chien,Wei-Chieh Hung,Rong-S 대한골다공증학회 2018 Osteoporosis and Sarcopenia Vol.4 No.2

        Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.

      • KCI등재

        Hepatocyte and mesenchymal stem cell co-transplantation in rats with acute liver failure

        Cheng-Maw Ho,Ya-Hui Chen,Chin-Sung Chien,Shu-Li Ho,Hui-Ling Chen,Rey-Heng Hu,Po-Huang Lee 대한이식학회 2020 Korean Journal of Transplantation Vol.34 No.2

        Background: Cell therapy is considered a potential alternative to liver transplantation in acute liver failure (ALF). We aimed to evaluate the add-on therapeutic benefit of hepatocyte and mesenchymal stem cell (MSC) cotransplantation over hepatocyte-only transplantations in a rat model of ALF. Methods: ALF was induced by D-galactosamine in Sprague-Dawley rats. Freshly isolated donor hepatocytes were derived from Tg (UBC-emGFP) rats and MSCs were collected from the bone marrow cells of DsRed rats. Donor hepatocytes (1×107/mL) were intraportally transplanted 24 hours after treatment with D-galactosamine over a 70-second interval, and donor MSCs (0.5, 1, or 2×106/0.5 mL) were intraportally transplanted 1 hour after the hepatocyte transplantation was complete. Animals were sacrificed after 7 and 14 days and subjected to donor cell identification, liver histology, serologic testing, and immunohistopathological examination. Results: MSCs were observed in the periportal area, 1 and 2 weeks after transplantation. Transplanted hepatocytes did not actively proliferate when compared to hepatocyte-only transplantation. Morphologically, transplanted MSCs did not appear to differentiate into hepatocytes even 2 weeks after transplantation. Cotransplantation of MSCs was associated with lower macrophage infiltration, and reduced type I collagen, hepatocyte growth factor, tumor necrosis factor-α, and interleukin 10 expression, with similar gene expression profiles for epidermal growth factor and interleukin 6, when compared to hepatocyte-only transplantation. Conclusions: Hepatocyte and MSC cotransplantation is feasible and safe in rat models of ALF. MSCs were found to survive the process and could be located within the periportal niches 2 weeks after treatment, without enhancing transplanted hepatocyte proliferation or differentiating into hepatocytes, while ameliorating the inflammatory response.

      • Histopathological Evidence for the Existence of Primary Liver Progenitor Cell Cancer: Insight from Cancer Stem Cell Pathobiology

        ( Cheng-maw Ho ),( Shu-li Ho ),( Chia-tung Shun ),( Po-huang Lee ),( Ya-hui Chen ),( Chin-sung Chien ),( Hui-ling Chen ),( Rey-heng Hu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Primary liver progenitor cell cancer is a rare disease entity without definite evidence and characterization. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this kind of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. Methods: Surgical specimens from primary liver cancer which posed diagnostic difficulty fitting within current WHO classification of combined hepatocellular-cholangiocellular carcinoma with stem-cell features according to the growth morphology and its suggested immunohistochemical features, were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes. Comparative interpretation of images was processed considering the histological morphology and characteristic markers. Results: The primary liver cancer consisted of CD24+ cancer progenitor cells and CD90+ mesenchymal stromal cells, which were intimately mixed. CD24+ cancer cells demonstrated bi-directional trends of differentiation: bile ductule transformation (cytokeratin 19+, epithelial cell adhesion molecule [EpCAM]+, neural cell adhesion molecule [NCAM]+, CD133+, and delta-like 1 homolog [DLK1]+); and trabecular or nested cell clusters toward hepatic lineage (hepatocyte nuclear factor-4 alpha [HNF-4α]+, Hep Par1+ and negative for CK19, EpCAM, CD133, and DLK1). Moderate lymphocyte (mostly CD4+ and CD8+ T cells) infiltrated in the CD90+ cancer- associated stroma. Conclusions: We provided the corroboration that liver progenitor cells can form primary liver cancer, not just presented as few side population of cancer stem cells. Its existence might pose significance for future stem cell therapeutic intervention targeting liver diseases, albeit the disease is rare.

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