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hepatocyte differentiation

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https://www.readbyqxmd.com/read/28431974/unique-mitochondrial-localization-of-arginase-1-and-2-in-hepatocytes-of-air-breathing-walking-catfish-clarias-batrachus-and-their-differential-expression-patterns-under-hyper-ammonia-stress
#1
Bodhisattwa Banerjee, Debaprasad Koner, Priyanka Lal, Nirmalendu Saha
Arginase (ARG) catalyzes the final step of ornithine-urea cycle (OUC) leading to a conversion of L-arginine to L-ornithine and urea. Several isoforms of ARG have been reported in vertebrates, out of which the two predominant isoforms are the cytosolic ARG1 and the mitochondrial ARG2. The air-breathing walking catfish (Clarias batrachus) is frequently being challenged by different environmental insults such as hyper-ammonia, dehydration and osmotic stresses in their natural habitats throughout the year. The present study investigated the active presence of ARG1 and ARG2 isoforms in hepatocytes along with unique localization of both the isoforms inside the mitochondria, and also their specific expression patterns under hyper-ammonia stress (5mM NH4Cl) in isolated hepatocytes of walking catfish...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28429746/the-small-g-protein-arf6-expressed-in-keratinocytes-by-hgf-stimulation-is-a-regulator-for-skin-wound-healing
#2
Yuki Miura, Van Ngo Thai Bich, Momoko Furuya, Hiroshi Hasegawa, Satoru Takahashi, Naohiro Katagiri, Tsunaki Hongu, Yuji Funakoshi, Norihiko Ohbayashi, Yasunori Kanaho
The earlier step of cutaneous wound healing process, re-epithelialization of the wounded skin, is triggered by a variety of growth factors. However, molecular mechanisms through which growth factors trigger skin wound healing are less understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is essential for the skin wound healing. Arf6 mRNA expression was dramatically induced in keratinocytes at the wounded skin, which was specifically suppressed by the c-Met inhibitor...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427343/loss-of-pericyte-smoothened-activity-in-mice-with-genetic-deficiency-of-leptin
#3
Guanhua Xie, Marzena Swiderska-Syn, Mark L Jewell, Mariana Verdelho Machado, Gregory A Michelotti, Richard T Premont, Anna Mae Diehl
BACKGROUND: Obesity is associated with multiple diseases, but it is unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that is coupled to energy availability at the cellular level. The satiety factor, leptin, is a key component of the sensor that matches cellular energy utilization to available energy supplies. Leptin deficiency signals energy depletion, whereas activating the Hedgehog pathway drives energy-consuming activities...
April 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28423990/self-assembled-nanogel-of-cholesterol-bearing-xyloglucan-as-a-drug-delivery-nanocarrier
#4
Shin-Ichi Sawada, Hiroko Yukawa, Shigeo Takeda, Yoshihiro Sasaki, Kazunari Akiyoshi
Xyloglucan (XG) is a multibranched polysaccharide consisting of a main chain β-1,4-glucan with xylose and galactose side chains. In this study, cholesterol-bearing XG (CHXG) was synthesized by the reaction of XG with cholesteryl N- (6-isocyanatohexyl) carbamate. The CHXG molecules self-assembled in water to form nanogels consisting of about 100 molecules of XG, and were characterized using differential light scattering and transmission electron microscopy. The number of cholesteryl groups per physical cross-linking site was estimated using a fluorescence quenching method...
April 20, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28416745/stable-h3-peptide-was-delivered-by-gold-nanorods-to-inhibit-lsd1-activation-and-induce-human-mesenchymal-stem-cells-differentiation
#5
Xin Meng, Jianping Li, Minjuan Zheng, Lei Zuo, Chao Sun, Yongsheng Zhu, Ling Fang, Liwen Liu, Xiaodong Zhou
Recently, lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, regulates post-translational modifications and has great promise as new targets for cancer and other diseases. Moreover, the ability of LSD1 to induce the differentiation of stem cells has attracted great attention in biological fields. In this study, we designed LSD1 peptide inhibitor based on its substrate H3 peptide. Through introducing a disulfide bond to stabilize the native peptide into alpha helical structure, we get a peptide with higher cell permeability and stability compared to its parent form...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414286/-pcr-analysis-of-the-absolute-number-of-copies-of-human-chromosome-18-transcripts-in-liver-and-hepg2-cells
#6
Y Y Kiseleva, K G Ptitsyn, O V Tikhonova, S P Radko, L K Kurbatov, I V Vakhrushev, V G Zgoda, E A Ponomarenko, A V Lisitsa, A I Archakov
Using reverse transcription in conjunction with the quantitative real-time PCR or digital droplet PCR, the transcriptome profiling of human chromosome 18 has been carried out in liver hepatocytes and hepatoblastoma cells (HepG2 cell line) in terms of the absolute number of each transcript per cell. The transcript abundance varies within the range of 0.006 to 9635 and 0.011 to 4819 copies per cell for HepG2 cell line and hepatocytes, respectively. The expression profiles for genes of chromosome 18 in hepatocytes and HepG2 cells were found to significantly correlate: the Spearman's correlation coefficient was equal to 0...
March 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28413633/pluripotent-stem-cells-to-hepatocytes-the-journey-so-far
#7
Anwar A Palakkan, Jyoti Nanda, James A Ross
Over the past several years, there has been substantial progress in the field of regenerative medicine, which has enabled new possibilities for research and clinical application. For example, there are ongoing efforts directed at generating functional hepatocytes from adult-derived pluripotent cells for toxicity screening, generating disease models or, in the longer term, for the treatment of liver failure. In the present review, the authors summarise recent developments in regenerative medicine and pluripotent stem cells, the methods and tissues used for reprogramming and the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28412976/hepatic-population-derived-from-human-pluripotent-stem-cells-is-effectively-increased-by-selective-removal-of-undifferentiated-stem-cells-using-ym155
#8
Seok-Jin Kang, Young-Il Park, So-Ryeon Hwang, Hee Yi, Nga Tham, Hyun-Ok Ku, Jae-Young Song, Hwan-Goo Kang
BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and induced pluripotent stem cells are promising target cells for cell regenerative medicine together with recently advanced technology of in-vitro differentiation. However, residual undifferentiated stem cells (USCs) during in-vitro differentiation are considered a potential risk for development of cancer cells and nonspecific lineage cell types. In this study we observed that USCs still exist during hepatic differentiation, consequently resulting in poor quality of the hepatic population and forming teratoma in vivo...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28412296/impact-of-higher-order-heme-degradation-products-on-hepatic-function-and-hemodynamics
#9
Raphael A Seidel, Thierry Claudel, Franziska A Schleser, Navin K Ojha, Matthias Westerhausen, Sandor Nietzsche, Christoph Sponholz, Frans Cuperus, Sina M Coldewey, Stefan H Heinemann, Georg Pohnert, Michael Trauner, Michael Bauer
BACKGROUND& AIMS: While, traditionally, biliverdin and bilirubin are considered end products of heme catabolism, there is evidence for further degradation to diverse bioactive products. As such, Z-BOX A and Z-BOX B arise upon oxidation with unknown implications for hepatocellular function and integrity. We studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. METHODS: Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28409921/mesenchymal-stem-cells-seeded-regenerated-silk-fibroin-complex-matrices-for-liver-regeneration-in-an-animal-model-of-acute-liver-failure
#10
Lijuan Xu, Shufang Wang, Xiang Sui, Yu Wang, Yinan Su, Li Huang, Yunwei Zhang, Zheng Chen, Qianqian Chen, Haitao Du, Yaopeng Zhang, Li Yan
The shortage of organ donation is the main limitation to liver transplantation as a treatment for the end-stage liver disease or acute liver failure. In order to develop an alternative therapy for acute liver failure, mesenchymal stem cells (MSCs) seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form scaffolds complex, respectively...
April 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28406695/visfatin-is-actively-secreted-in-vitro-from-u-937-macrophages-but-only-passively-released-from-3t3-l1-adipocytes-and-hepg2-hepatocytes
#11
P Svoboda, E KříŽová, K Čeňková, K Vápenková, J Zídková, V Zídek, V Škop
Visfatin is a multi-functional molecule that can act intracellularly and extracellularly as an adipokine, cytokine and enzyme. One of the main questions concerning visfatin is the mechanism of its secretion; whether, how and from which cells visfatin is released. The objective of this in vitro study was to observe the active secretion of visfatin from 3T3-L1 preadipocytes and adipocytes, HepG2 hepatocytes, U-937, THP-1 and HL-60 monocytes and macrophages. The amount of visfatin in media and cell lysate was always related to the intracellular enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), to exclude the passive release of visfatin...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28406324/evolving-paradigm-of-treatment-for-autoimmune-hepatitis
#12
Albert J Czaja
Current medications for autoimmune hepatitis have broad anti-inflammatory and immunosuppressive actions, and their effects are short-lived and inconsistent. The goals of this review were to describe the actions and shortcomings of these medications, indicate the key pathogenic mechanisms that might be targeted by site-directed interventions, and present the pivotal studies supporting development of these alternative agents. Areas covered: Abstracts cited in PubMed from April 1964 to February 2017 were identified using the search words "treatment of autoimmune hepatitis"...
April 13, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28397810/hepatocytic-parental-progenitor-cells-of-rat-small-hepatocytes-maintain-self-renewal-capability-after-long-term-culture
#13
Masayuki Ishii, Junichi Kino, Norihisa Ichinohe, Naoki Tanimizu, Takafumi Ninomiya, Hiromu Suzuki, Toru Mizuguchi, Koichi Hirata, Toshihiro Mitaka
The liver has a variety of functions for maintaining homeostasis, and hepatocytes play a major role. In contrast with the high regenerative capacity of mature hepatocytes (MHs) in vivo, they have not been successfully expanded ex vivo. Here we demonstrate that CD44-positive cells sorted from small hepatocyte (SH) colonies derived from a healthy adult rat liver can proliferate on a Matrigel-coated dish in serum-free chemically defined medium; in addition, a subpopulation of the cells can divide more than 50 times in a period of 17 weeks every 4-week-passage...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396610/modulation-of-glucose-metabolism-by-a-natural-compound-from-chloranthus-japonicus-via-activation-of-amp-activated-protein-kinase
#14
Rongkuan Hu, Huan Yan, Xiaoyan Fei, Haiyang Liu, Jiarui Wu
AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose metabolism. Here, we demonstrated that shizukaol F, a natural compound isolated from Chloranthus japonicus, can activate AMPK and modulate glucose metabolism both in vitro and in vivo. Shizukaol F increased glucose uptake in differentiated C2C12 myotubes by stimulating glucose transporter-4 (GLUT-4) membraned translocation. Treatment of primary mouse hepatocytes with shizukaol F decreased the expression of phosphoenolpyruvate carboxykinase 2 (PEPCK), glucose-6-phosphatase (G6Pase) and suppressed hepatic gluconeogenesis...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#15
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28396286/altered-mitochondrial-and-peroxisomal-integrity-in-lipocalin-2-deficient-mice-with-hepatic-steatosis
#16
Anastasia Asimakopoulou, Annabelle Fülöp, Erawan Borkham-Kamphorst, Eddy Van de Leur, Nikolaus Gassler, Thorsten Berger, Birte Beine, Helmut E Meyer, Tak W Mak, Carsten Hopf, Corinna Henkel, Ralf Weiskirchen
Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis, we performed a comparative profiling of proteins and lipids of wild type (WT) and Lcn2-deficient mice fed either standard chow or a methionine- and choline-deficient (MCD) diet...
April 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28394260/hepatocyte-nuclear-factor-1%C3%AE-suppresses-steatosis-associated-liver-cancer-by-inhibiting-ppar%C3%AE-transcription
#17
Cecilia Patitucci, Gabrielle Couchy, Alessia Bagattin, Tatiana Cañeque, Aurélien de Reyniès, Jean-Yves Scoazec, Raphaël Rodriguez, Marco Pontoglio, Jessica Zucman-Rossi, Mario Pende, Ganna Panasyuk
Worldwide epidemics of metabolic diseases, including liver steatosis, are associated with an increased frequency of malignancies, showing the highest positive correlation for liver cancer. The heterogeneity of liver cancer represents a clinical challenge. In liver, the transcription factor PPARγ promotes metabolic adaptations of lipogenesis and aerobic glycolysis under the control of Akt2 activity, but the role of PPARγ in liver tumorigenesis is unknown. Here we have combined preclinical mouse models of liver cancer and genetic studies of a human liver biopsy atlas with the aim of identifying putative therapeutic targets in the context of liver steatosis and cancer...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28390928/itraconazole-cis-diastereoisomers-activate-aryl-hydrocarbon-receptor-ahr-and-pregnane-x-receptor-pxr-and-induce-cyp1a1-in-human-cell-lines-and-human-hepatocytes
#18
Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR...
April 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28389020/seeds-in-the-liver
#19
REVIEW
Hongjie Ji, Yanrong Lu, Yujun Shi
The liver is a crucial organ for homeostasis and has a tremendous self-renewal and regenerative capacity. It has long been believed that the self-renewal and repair of the liver within a given physiological condition or its repopulation in chronic liver diseases, when hepatocyte proliferation is impaired, will primarily be conducted by the proliferating duct cells, termed "oval cells" or hepatic progenitor cells (HPCs). In addition, numerous studies have revealed that HPCs are the initial tumor cells of liver cancer under certain micro-environments...
April 4, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28388431/induced-pluripotent-stem-cell-differentiation-enables-functional-validation-of-gwas-variants-in-metabolic-disease
#20
Curtis R Warren, John F O'Sullivan, Max Friesen, Caroline E Becker, Xiaoling Zhang, Poching Liu, Yoshiyuki Wakabayashi, Jordan E Morningstar, Xu Shi, Jihoon Choi, Fang Xia, Derek T Peters, Mary H C Florido, Alexander M Tsankov, Eilene Duberow, Lauren Comisar, Jennifer Shay, Xin Jiang, Alexander Meissner, Kiran Musunuru, Sekar Kathiresan, Laurence Daheron, Jun Zhu, Robert E Gerszten, Rahul C Deo, Ramachandran S Vasan, Christopher J O'Donnell, Chad A Cowan
Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures...
April 6, 2017: Cell Stem Cell
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