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1

Mundiri, Nur Azmiati, Meta Maulida Damayanti, Maya Tejasari, Annisa Rahmah Furqaani, and R. A. Retno Ekowati. "Pengaruh Fraksi Air Buah Lemon terhadap Gambaran Morfologi Jaringan Hati Mencit Tua yang Diberi Pakan Tinggi Lemak." Jurnal Integrasi Kesehatan & Sains 1, no. 1 (2019): 49–53. http://dx.doi.org/10.29313/jiks.v1i1.4321.

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Dislipidemia merupakan salah satu faktor risiko dari non alcoholic fatty liver disease (NAFLD). NAFLD mempunyai karakteristik steatosis hepatik, hepatocyte ballooning, inflamasi lobular, dan fibrosis. Kandungan flavonoid pada Citrus limon dipercaya dapat mencegah steatosis hepatik. Tujuan penelitian ini mengetahui pengaruh fraksi air buah lemon terhadap gambaran morfologi jaringan hati mencit tua yang diberi pakan tinggi lemak. Penelitian ini merupakan penelitian eksperimental dengan subjek penelitian adalah mencit (Mus musculus) jantan galur DDY tua yang dibagi menjadi empat kelompok secara a
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2

Sibuea, Christine Verawaty, Enjelin Sasa Kristanti Hutabarat, and David M. T. Simangunsong. "Viabilitas Hepatosit pada Monokultur 3D Metode Hanging Drop dan Monokultur 2D." Nommensen Journal of Medicine 7, no. 2 (2022): 36–38. http://dx.doi.org/10.36655/njm.v7i2.623.

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Background: Liver is a vital organ that has many functions including metabolism, detoxification of toxins and protein synthesis. The prevalence of liver disease is high and the treatment of liver disease continues to develop, so liver models are needed to study liver disease mechanisms and test drug toxicity. Many hepatocyte culture methods are being developed to construct an optimal liver model. The best culture method maintains high hepatocyte viability.
 Objective : This study aims to determine the viability of hepatocytes in 3D hanging drop method culture and in 2D culture.
 Meth
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3

Skuratov, A. G., D. R. Petrenyov, and A. N. Kondrachuk. "EXPRESSION OF MARKER GENES BY HEPATOCYTE-LIKE CELLS differentiated from mesenchymal stem cells." Health and Ecology Issues, no. 3 (September 28, 2013): 105–10. http://dx.doi.org/10.51523/2708-6011.2013-10-3-22.

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Objective: to investigate the expression of marker genes by hepatocyte-like cells differentiated from mesenchymal stem cells (MSCs). Materials and methods. Wistar white rats, bone marrow MSCs, isolated hepatocytes of the rats were obtained by enzymatic perfusion of liver; differentiation of MSCs in hepatocyte direction; light microscopy; investigation of expression of genes by polymerase chain reaction (PCR). Results. The observed changes in the gene expression profile during the stages of differentiation indicate the presence of the cells differentiated into hepatocytic direction in MSCs cult
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4

Sibuea, Christine Verawaty, Jeanne Adiwinata Pawitan, and Radiana Antarianto. "Pengaruh Penggantian Medium terhadap Viabilitas Hepatosit Kultur 3D Organoid Hati." Nommensen Journal of Medicine 7, no. 2 (2022): 39–42. http://dx.doi.org/10.36655/njm.v7i2.625.

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Background : Liver organoids can be used as materials for Bioartificial Liver, to study the mechanism of liver disease and as drug test toxicity. Reconstruction of liver organoids requires optimal culture methods, culture medium and cellular components to construct liver organoids that resemble liver microstructure in vivo with optimal function. 3D culture method using hepatocytes and stem cells with PRP supplemented William's E can reconstruct liver organoids with liver function. Medium exchange is an usual method to maintain the required nutrients and to eliminate waste products, but it requ
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5

Gómez-Aristizábal, Alejandro, and John Edward Davies. "The effects of human umbilical cord perivascular cells on rat hepatocyte structure and functional polarity." Biochemistry and Cell Biology 91, no. 3 (2013): 140–47. http://dx.doi.org/10.1139/bcb-2012-0079.

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Hepatocyte culture is a useful tool for the study of their biology and the development of bioartificial livers. However, many challenges have to be overcome since hepatocytes rapidly lose their normal phenotype in vitro. We have recently demonstrated that human umbilical cord perivascular cells (HUCPVCs) are able to provide support to hepatocytes. In the present study we go further into exploring the effects that HUCPVCs have in the functional polarization, and both the internal and external organization, of hepatocytes. Also, we investigate HUCPVC–hepatocyte crosstalk by tracking both the eff
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6

Naruse, K., Y. Sakai, I. Nagashima, G. X. Jiang, M. Suzuki, and T. Muto. "Comparisons of Porcine Hepatocyte Spheroids and Single Hepatocytes in the Non-Woven Fabric Bioartificial Liver Module." International Journal of Artificial Organs 19, no. 10 (1996): 605–9. http://dx.doi.org/10.1177/039139889601901008.

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We previously developed a new bioreactor of the bioartificial liver composed of non-woven fabric. We have also experimented with hepatocyte spheroids, with the aim of improving the efficiency of this NWF bioreactor. In this study, we compared the efficiencies of NWF bioreactors employing hepatocyte spheroids versus single hepatocytes. Hepatocytes were isolated from a whole pig liver by Seglen's method. 1.0 × 1010 single hepatocytes were immobilized in the NWF bioreactor. Another 1.0 × 1010 hepatocytes were allowed to form spheroids by 24 hr suspension culture in a 4-L culture vessel, before be
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7

Mason, William S., Chunxiao Xu, Huey Chi Low, et al. "The Amount of Hepatocyte Turnover That Occurred during Resolution of Transient Hepadnavirus Infections Was Lower When Virus Replication Was Inhibited with Entecavir." Journal of Virology 83, no. 4 (2008): 1778–89. http://dx.doi.org/10.1128/jvi.01587-08.

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ABSTRACT Transient hepadnavirus infections can involve spread of virus to the entire hepatocyte population. In this situation hepatocytes present following recovery are derived from infected hepatocytes. During virus clearance antiviral cytokines are thought to block virus replication and formation of new covalently closed circular DNA (cccDNA), the viral transcriptional template. It remains unclear if existing cccDNA is eliminated noncytolytically or if hepatocyte death and proliferation, to compensate for killing of some of the infected hepatocytes, are needed to remove cccDNA from surviving
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8

Gupta, Sanjeev, Pankaj Rajvanshi, Emma Aragona, Chang-Don Lee, Purnachandra R. Yerneni, and Robert D. Burk. "Transplanted hepatocytes proliferate differently after CCl4 treatment and hepatocyte growth factor infusion." American Journal of Physiology-Gastrointestinal and Liver Physiology 276, no. 3 (1999): G629—G638. http://dx.doi.org/10.1152/ajpgi.1999.276.3.g629.

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To understand regulation of transplanted hepatocyte proliferation in the normal liver, we used genetically marked rat or mouse cells. Hosts were subjected to liver injury by carbon tetrachloride (CCl4), to liver regeneration by a two-thirds partial hepatectomy, and to hepatocellular DNA synthesis by infusion of hepatocyte growth factor for comparative analysis. Transplanted hepatocytes were documented to integrate in periportal areas of the liver. In response to CCl4 treatments after cell transplantation, the transplanted hepatocyte mass increased incrementally, with the kinetics and magnitude
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9

Pastor, Catherine M., and Valérie Vilgrain. "Steatosis Alters the Activity of Hepatocyte Membrane Transporters in Obese Rats." Cells 10, no. 10 (2021): 2733. http://dx.doi.org/10.3390/cells10102733.

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Fat accumulation (steatosis) in ballooned hepatocytes alters the expression of membrane transporters in Zucker fatty (fa/fa) rats. The aim of the study was to quantify the functions of these transporters and their impact on hepatocyte concentrations using a clinical hepatobiliary contrast agent (Gadobenate dimeglumine, BOPTA) for liver imaging. In isolated and perfused rat livers, we quantified BOPTA accumulation and decay profiles in fa/+ (normal) and fa/fa hepatocytes by placing a gamma counter over livers. Profiles of BOPTA accumulation and decay in hepatocytes were analysed with nonlinear
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10

GHIURCO, Ioan Florin, Aurel DAMIAN, Vasile Florin RUS, et al. "Mitochondria Load Degree in Hepatocytes of the Classical Hepatic Lobules in Chinchilla (Chinchilla lanigera)." Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine 78, no. 1 (2021): 76. http://dx.doi.org/10.15835/buasvmcn-m:2021.0004.

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Hepatocytes represent the majority of the liver cell population and are arranged in the form of cords placed in intimate contact with the sinusoidal capillaries. The functional complexity corroborated with the intensity of the activity of hepatocytes requires large amounts of energy. The organelles involved in the production of chemical energy used in the activity of hepatocytes are the mitochondria. The purpose of this study was to verify the mitochondrial load of hepatocytes in all areas of the classical hepatic lobules, in order to indirectly assess the intensity of hepatocyte activity in e
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11

Lilja, Helene, Pierre Blanc, Achilles A. Demetriou, and Jacek Rozga. "Response of Cultured Fetal and Adult Rat Hepatocytes to Growth Factors and Cyclosporine." Cell Transplantation 7, no. 3 (1998): 257–66. http://dx.doi.org/10.1177/096368979800700304.

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Hepatocyte transplantation is a promising alternative to orthotopic liver transplantation in experimental animal models with genetic disorders of liver metabolism and liver failure. Fetal hepatocytes have several characteristics that make them potentially suitable as donor cells. In contrast to adult hepatocytes, fetal hepatocytes are thought to be highly proliferative, which may facilitate engraftment, expansion of transplanted cell population, and gene transfer requiring active DNA synthesis. The present study was undertaken to evaluate the proliferative capacity of fetal and adult rat hepat
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12

Rivas, Pedro A., Alfredo J. Fabrega, Daniel Schwartz, et al. "Transplantation of Hepatocytes: An In-Vitro and In-Vivo Study in Canines." Cell Transplantation 3, no. 2 (1994): 193–201. http://dx.doi.org/10.1177/096368979400300208.

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We isolated and transplanted hepatocytes in the canine, large animal model to evaluate hepatocyte yield and purity as well as the optimal site for hepatocyte engraftment (i.e., the spleen or the portal bed). We obtained viable, pure, single hepatocyte suspensions that were readily preserved at 4°C in University of Wisconsin (UW) solution for up to 3 days. Both intrasplenic and portal vein injection were well tolerated, with minimal recipient morbidity and mortality when 1-2 × 109 hepatocytes were injected into immunosuppressed allogeneic hosts. We noted the embolization of hepatocytes into the
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13

Garcı́a, Fabiana, Arlinet Kierbel, M. Cecilia Larocca, et al. "The Water Channel Aquaporin-8 Is Mainly Intracellular in Rat Hepatocytes, and Its Plasma Membrane Insertion Is Stimulated by Cyclic AMP." Journal of Biological Chemistry 276, no. 15 (2001): 12147–52. http://dx.doi.org/10.1074/jbc.m009403200.

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We previously found that water transport across hepatocyte plasma membranes occurs mainly via a non-channel mediated pathway. Recently, it has been reported that mRNA for the water channel, aquaporin-8 (AQP8), is present in hepatocytes. To further explore this issue, we studied protein expression, subcellular localization, and regulation of AQP8 in rat hepatocytes. By subcellular fractionation and immunoblot analysis, we detected anN-glycosylated band of ∼34 kDa corresponding to AQP8 in hepatocyte plasma and intracellular microsomal membranes. Confocal immunofluorescence microscopy for AQP8 in
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14

Sun, D., Y. Gong, H. Kojima, et al. "Increasing cell membrane potential and GABAergic activity inhibits malignant hepatocyte growth." American Journal of Physiology-Gastrointestinal and Liver Physiology 285, no. 1 (2003): G12—G19. http://dx.doi.org/10.1152/ajpgi.00513.2002.

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Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with a fluorescent voltage-sensitive dye and GABAA receptor e
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15

Aurich, Hendryk, Sarah Koenig, Christian Schneider, et al. "Functional Characterization of Serum-Free Cultured Rat Hepatocytes for Downstream Transplantation Applications." Cell Transplantation 14, no. 7 (2005): 497–506. http://dx.doi.org/10.3727/000000005783982855.

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Although ex vivo culture of hepatocytes is known to impair functionality, it may still be considered as desirable to propagate or manipulate them in culture prior to transplantation into the host liver. The aim of this study was to clarify whether rat hepatocytes cultured over different periods of time proliferate and retain their hepatocyte-specific functions following transplantation into the recipient liver. Rat hepatocytes were cultured under serum-free conditions in the presence of hepatocyte and epidermal growth factors. Cells derived from wild-type donor livers were transplanted into th
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16

Peng, Weng Chuan, Lianne J. Kraaier, and Thomas A. Kluiver. "Hepatocyte organoids and cell transplantation: What the future holds." Experimental & Molecular Medicine 53, no. 10 (2021): 1512–28. http://dx.doi.org/10.1038/s12276-021-00579-x.

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AbstractHistorically, primary hepatocytes have been difficult to expand or maintain in vitro. In this review, we will focus on recent advances in establishing hepatocyte organoids and their potential applications in regenerative medicine. First, we provide a background on the renewal of hepatocytes in the homeostatic as well as the injured liver. Next, we describe strategies for establishing primary hepatocyte organoids derived from either adult or fetal liver based on insights from signaling pathways regulating hepatocyte renewal in vivo. The characteristics of these organoids will be describ
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17

Afford, Simon C., Satinder Randhawa, Aristides G. Eliopoulos, Stefan G. Hubscher, Lawrence S. Young, and David H. Adams. "CD40 Activation Induces Apoptosis in Cultured Human Hepatocytes via Induction of Cell Surface Fas Ligand Expression and Amplifies Fas-mediated Hepatocyte Death during Allograft Rejection." Journal of Experimental Medicine 189, no. 2 (1999): 441–46. http://dx.doi.org/10.1084/jem.189.2.441.

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We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68+ macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the He
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18

Chang, Tian, Ji, et al. "Single-Cell Transcriptomes Reveal Characteristic Features of Mouse Hepatocytes with Liver Cholestatic Injury." Cells 8, no. 9 (2019): 1069. http://dx.doi.org/10.3390/cells8091069.

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Hepatocytes are the main parenchymal cells of the liver and play important roles in liver homeostasis and disease process. The heterogeneity of normal hepatocytes has been reported, but there is little knowledge about hepatocyte subtype and distinctive functions during liver cholestatic injury. Bile duct ligation (BDL)-induced mouse liver injury model was employed, and single-cell RNA sequencing was performed. Western blot and qPCR were used to study gene expression. Immunofluoresence was employed to detect the expressions of marker genes in hepatocytes. We detected a specific hepatocyte clust
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19

Kobayashi, Naoya, and Noriaki Tanaka. "Engineering of Human Hepatocyte Lines for Cell Therapies in Humans: Prospects and Remaining Hurdles." Cell Transplantation 11, no. 5 (2002): 417–20. http://dx.doi.org/10.3727/000000002783985693.

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Hepatocyte-based biological therapies are increasingly envisioned for temporary support in acute liver failure and provision of specific-liver functions in liver-based metabolic deficiency. One of the hurdles to develop such therapies is severe shortage of human livers for hepatocyte isolation. To address the issue, we have focused on reversible immortalization of human hepatocytes. Such technology can allow rapid preparation of functional and uniform human hepatocytes. Here we present our strategy to construct transplantable human hepatocyte cell lines.
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Lu, Na, Yun Liu, An Tang, Lulu Chen, Dengshun Miao та Xiaoqin Yuan. "Hepatocyte-Specific Ablation of PP2A Catalytic SubunitαAttenuates Liver Fibrosis Progression via TGF-β1/Smad Signaling". BioMed Research International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/794862.

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Protein phosphatase 2A (PP2A), a family of the major serine/threonine phosphatases in cells, regulates many aspects of physiological processes. However, isoform-specific substrates and the biological role of each specific member of the PP2A family remain largely unknown. In this study, we investigated whether PP2A catalytic subunit Cα(PP2Acα) is involved in chronic hepatic injury and fibrosis. A hepatocyte-specific PP2Acαablation mice model was established to examine the effect of PP2Acαon carbon tetrachloride- (CCl4-) induced chronic hepatic injury and fibrosis. Our results showed that PP2Acα
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Aoki, Takeshi, Tomotake Koizumi, Yasuna Kobayashi, et al. "A Novel Method of Cryopreservation of Rat and Human Hepatocytes by Using Encapsulation Technique and Possible Use for Cell Transplantation." Cell Transplantation 14, no. 9 (2005): 609–20. http://dx.doi.org/10.3727/000000005783982710.

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Encapsulated hepatocyte transplantation is a promising approach to cell transplantation without immunosuppression as an alternative to whole organ liver transplantation. However, the shortage of donor cells for hepatocyte transplantation has not been resolved, and at this critical point, it seems necessary to establish a method of hepatocyte cryopreservation to allow clinical application of hepatocyte transplantation and the development of a bioartificial liver system in the near future. In this study we demonstrated that cryopreserved microencapsulated rat and human hepatocytes can retain the
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22

Mason, William S., Allison R. Jilbert, and Samuel Litwin. "Hepatitis B Virus DNA Integration and Clonal Expansion of Hepatocytes in the Chronically Infected Liver." Viruses 13, no. 2 (2021): 210. http://dx.doi.org/10.3390/v13020210.

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Human hepatitis B virus (HBV) can cause chronic, lifelong infection of the liver that may lead to persistent or episodic immune-mediated inflammation against virus-infected hepatocytes. This immune response results in elevated rates of killing of virus-infected hepatocytes, which may extend over many years or decades, lead to fibrosis and cirrhosis, and play a role in the high incidence of hepatocellular carcinoma (HCC) in HBV carriers. Immune-mediated inflammation appears to cause oxidative DNA damage to hepatocytes, which may also play a major role in hepatocarcinogenesis. An additional DNA
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23

Kang, Sun Woo Sophie, Victoria C. Cogger, David G. Le Couteur, and Dong Fu. "Multiple cellular pathways regulate lipid droplet homeostasis for the establishment of polarity in collagen sandwich-cultured hepatocytes." American Journal of Physiology-Cell Physiology 317, no. 5 (2019): C942—C952. http://dx.doi.org/10.1152/ajpcell.00051.2019.

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Hepatocyte polarization is energy dependent. The establishment of polarization in collagen sandwich culture of hepatocytes requires utilization of lipid droplets and mitochondrial β-oxidation to supply ATP. Multiple cellular pathways are involved in lipid droplet homeostasis; however, mechanistic insights of how hepatocytes utilize lipid droplets during polarization remain elusive. The current study investigated the effects of various pathways involved in lipid droplet homeostasis on bioenergetics during hepatocyte polarization. The results showed that hepatocytes were dependent on lipolysis o
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Tolosa, Laia, Eugenia Pareja-Ibars, M. Teresa Donato, et al. "Neonatal Livers: A Source for the Isolation of Good-Performing Hepatocytes for Cell Transplantation." Cell Transplantation 23, no. 10 (2014): 1229–42. http://dx.doi.org/10.3727/096368913x669743.

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Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. However, the supply of hepatocytes is limited given the shortage of organs available to isolate good-functioning quality cells. Neonatal livers may be a potential source alternative to adult livers to obtain good-performing hepatic cells for hepatocyte transplantation, which has not yet been explored profoundly. High-yield preparations of viable hepatocytes were isolated from 1- to 23-day-old liver donors, cryopreserved, and banked. Cell integrity and functional quality
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25

Ju, Wenjun, Atsushi Ogawa, Joerg Heyer, et al. "Deletion of Smad2 in Mouse Liver Reveals Novel Functions in Hepatocyte Growth and Differentiation." Molecular and Cellular Biology 26, no. 2 (2006): 654–67. http://dx.doi.org/10.1128/mcb.26.2.654-667.2006.

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ABSTRACT Smad family proteins Smad2 and Smad3 are activated by transforming growth factor β (TGF-β)/activin/nodal receptors and mediate transcriptional regulation. Although differential functional roles of Smad2 and Smad3 are apparent in mammalian development, the relative functional roles of Smad2 and Smad3 in postnatal systems remain unclear. We used Cre/loxP-mediated gene targeting for hepatocyte-specific deletion of Smad2 (S2HeKO) in adult mice and generated hepatocyte-selective Smad2/Smad3 double knockouts by intercrossing AlbCre/Smad2f/f (S2HeKO) and Smad3-deficient Smad3ex8/ex8 (S3KO) m
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26

Bluhme, Emil, Ewa Henckel, Roberto Gramignoli, et al. "Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death." Cell Transplantation 31 (January 2022): 096368972110699. http://dx.doi.org/10.1177/09636897211069900.

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Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015–2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy perfor
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27

Ambrosino, Giovanni, Stefano M. M. Basso, Sergio Varotto, Enrico Zardi, Antonio Picardi, and Davide F. D'amico. "Isolated Hepatocytes versus Hepatocyte Spheroids: In Vitro Culture of Rat Hepatocytes." Cell Transplantation 14, no. 6 (2005): 397–401. http://dx.doi.org/10.3727/000000005783982954.

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The use of hepatocytes that express liver-specific functions to develop an artificial liver is promising. Unfortunately, the loss of specialized liver functions (dedifferentiation) is still a major problem. Different techniques, such as collagen entrapment, spherical multicellular aggregates (spheroids), and coculture of hepatocytes with extracellular matrix, have been used to improve the performance of hepatocytes in culture. The aim of this study was to compare two different models of hepatocyte isolation in culture: isolated hepatocytes (G1) and hepatocyte spheroids (60% hepatocytes, 40% no
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Wilson, D., and J. D. Yarbrough. "Autoradiographic analysis of hepatocytes in mirex-induced adaptive liver growth." American Journal of Physiology-Gastrointestinal and Liver Physiology 255, no. 1 (1988): G132—G139. http://dx.doi.org/10.1152/ajpgi.1988.255.1.g132.

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The relationships between [3H]thymidine incorporation into hepatocyte nuclei, cell enlargement, and mitotic index were studied in intact (INT) and adrenalectomized (ADX) mirex-dosed rats. In INT mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear labeling of mononuclear hepatocytes with peaks at 48 and 66 h postmirex dose, a peak in mitotic activity 66 h postmirex dose, and a significant increase in binuclear hepatocyte size 48 h postmirex dose. In ADX mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear label
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29

Catapano, G., L. DE Bartolo, C. P. Lombardi, and E. Drioli. "The Effect of Catabolite Concentration on the Viability and Functions of Isolated Rat Hepatocytes." International Journal of Artificial Organs 19, no. 4 (1996): 245–50. http://dx.doi.org/10.1177/039139889601900407.

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The treatment of patients with hepatic failure by means of hybrid liver support devices using primary xenogeneic hepatocytes is currently hindered by the rapid loss of cell metabolic functions. Similarly to what happens with other mammalian cells, accumulation of catabolites in the neighborhood of cultured hepatocytes might significantly affect their viability and functions. In this paper, we investigated the effects of high concentrations of catabolites, such as ammonia and lactic acid, on the viability and functions of rat hepatocytes cultured on collagen coated Petri dishes. The effects on
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30

Cui, Changhao, Shin Enosawa, Hitomi Matsunari, Hiroshi Nagashima, and Akihiro Umezawa. "Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo." International Journal of Molecular Sciences 20, no. 24 (2019): 6123. http://dx.doi.org/10.3390/ijms20246123.

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To improve the therapeutic potential of hepatocyte transplantation, the effects of the mitogen-activated protein kinase kinase 4 (MKK4) inhibitor, myricetin (3,3′,4′,5,5′,7-hexahydroxylflavone) were examined using porcine and human hepatocytes in vitro and in vivo. Hepatocytes were cultured, showing the typical morphology of hepatic parenchymal cell under 1–10 µmol/L of myricetin, keeping hepatocyte specific gene expression, and ammonia removal activity. After injecting the hepatocytes into neonatal Severe combined immunodeficiency (SCID) mouse livers, cell colony formation was found at 10–15
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31

Kaushansky, Alexis, Laura S. Austin, Sebastian A. Mikolajczak, et al. "Susceptibility to Plasmodium yoelii Preerythrocytic Infection in BALB/c Substrains Is Determined at the Point of Hepatocyte Invasion." Infection and Immunity 83, no. 1 (2014): 39–47. http://dx.doi.org/10.1128/iai.02230-14.

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After transmission byAnophelesmosquitoes,Plasmodiumsporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible toPlasmodium yoeliipreerythrocytic infection than BALB/cJ mice. This difference occurs at the level of early hepatocyte infection, bu
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32

Staricoff, M. A., R. D. Cohen, and J. P. Monson. "Carrier-mediated lactate entry into isolated hepatocytes from fed and starved rats: Zonal distribution and temperature dependence." Bioscience Reports 15, no. 2 (1995): 99–109. http://dx.doi.org/10.1007/bf01200144.

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We examined the possibility of quantitative differences in lactate entry into periportal and perivenous hepatocytes under different nutritional states. The rate of14C-L(+)-lactate uptake was determined after 15-second incubations with freshly isolated zonally separated hepatocytes using a centrifuge stop technique at 37 °C and 4 °C, in the presence or absence of either differing amounts of unlabelled lactate or of a hepatocyte lactate transport inhibitor,α-cyano-3-hydroxycinnamate. Total entry as well as carrier mediated entry of14C-L(+)-lactate into the isolated cell populations was found to
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33

Nussler, A. K., Z. Z. Liu, M. Di Silvio, et al. "Hepatocyte inducible nitric oxide synthesis is influenced in vitro by cell density." American Journal of Physiology-Cell Physiology 267, no. 2 (1994): C394—C401. http://dx.doi.org/10.1152/ajpcell.1994.267.2.c394.

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Hepatocyte plating density is known to affect cell function. Human and rat hepatocytes have been shown to express the inducible nitric oxide synthase (INOS) in response to cytokines plus lipopolysaccharide (LPS). The following studies were performed to determine the effects of hepatocyte plating density on the regulation of INOS. Rat hepatocytes were plated at densities from 10(4) to 20 x 10(4) hepatocytes/cm2 and stimulated with a combination of LPS, interferon-gamma, interleukin-1, and tumor necrosis factor. We found that NO2- plus NO3- released from stimulated hepatocytes declines with incr
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Minnis-Lyons, Sarah E., Sofía Ferreira-González, Niya Aleksieva, et al. "Notch-IGF1 signaling during liver regeneration drives biliary epithelial cell expansion and inhibits hepatocyte differentiation." Science Signaling 14, no. 688 (2021): eaay9185. http://dx.doi.org/10.1126/scisignal.aay9185.

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In the adult liver, a population of facultative progenitor cells called biliary epithelial cells (BECs) proliferate and differentiate into cholangiocytes and hepatocytes after injury, thereby restoring liver function. In mammalian models of chronic liver injury, Notch signaling is essential for bile duct formation from these cells. However, the continual proliferation of BECs and differentiation of hepatocytes in these models have limited their use for determining whether Notch signaling is required for BECs to replenish hepatocytes after injury in the mammalian liver. Here, we used a temporal
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Kato, Kazuya, W. John B. Hodgson, Nader G. Abraham, et al. "Expression and Inducibility of Cytochrome P450 Iiia Family within Intrasplenically Transplanted Fetal Hepatocytes." Cell Transplantation 5, no. 1 (1996): 117–22. http://dx.doi.org/10.1177/096368979600500116.

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With the development of transplantation of hepatocytes into the spleen, interest has focused on the metabolic changes associated with hepatocyte proliferation. As these changes are important for drug metabolism in hepatocytes, we examined the expression and inducibility of the cytochrome P450 IIIA family within transplanted hepatocytes. Fetal hepatocytes were harvested at 20 days of gestation from spontaneously hypertensive rats (SHRs) and transplanted into recipient adult SHR spleens. Microscopic examination of the recipient spleens 4 and 10 wk after transplantation revealed masses of hepatoc
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Sheng, Liang, Bijie Jiang, and Liangyou Rui. "Intracellular lipid content is a key intrinsic determinant for hepatocyte viability and metabolic and inflammatory states in mice." American Journal of Physiology-Endocrinology and Metabolism 305, no. 9 (2013): E1115—E1123. http://dx.doi.org/10.1152/ajpendo.00401.2013.

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The liver is an essential metabolic organ. In addition to metabolizing glucose and lipids, hepatocytes also secrete various cytokines that modulate both hepatocyte metabolism and liver inflammation. Hepatocyte injury and death and liver inflammation are the major contributors to liver diseases, including nonalcoholic steatohepatitis (NASH). Anatomic locations have a profound effect on hepatocyte metabolism, and liver zonation describes the metabolic heterogeneity of hepatocytes along the portovenous axis. However, it is unclear whether hepatocyte heterogeneity is affected by intrinsic factors
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Johnson, Lynt B., John Aiken, David Mooney, et al. "The Mesentery as a Laminated Vascular Bed for Hepatocyte Transplantation." Cell Transplantation 3, no. 4 (1994): 273–81. http://dx.doi.org/10.1177/096368979400300403.

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The small bowel mesentery provides a unique structure of a large vascularized surface area to support hepatocyte transplantation. Cell-seeded polymeric matrices can be juxtaposed in a relatively atraumatic manner between leaves of mesentery such that adequate exchange of nutrients and diffusion of gases can proceed in the interim while neovascularization occurs. Hepatocytes obtained from (RHA) Wistar rats by collagenase perfusion were seeded onto non-woven filamentous sheets of polyglycolic acid 1 × 3 cm in size and 2 mm thickness to a density of 500,000 cells/cm2. Twenty-six recipient Gunn ra
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Borkham-Kamphorst, Erawan, Ute Haas, Eddy Van de Leur, Anothai Trevanich, and Ralf Weiskirchen. "Chronic Carbon Tetrachloride Applications Induced Hepatocyte Apoptosis in Lipocalin 2 Null Mice through Endoplasmic Reticulum Stress and Unfolded Protein Response." International Journal of Molecular Sciences 21, no. 15 (2020): 5230. http://dx.doi.org/10.3390/ijms21155230.

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The lack of Lipocalin (LCN2) provokes overwhelming endoplasmic reticulum (ER) stress responses in vitro and in acute toxic liver injury models, resulting in hepatocyte apoptosis. LCN2 is an acute phase protein produced in hepatocytes in response to acute liver injuries. In line with these findings we investigated ER stress responses of Lcn2−/− mice in chronic ER stress using a long-term repetitive carbon tetrachloride (CCl4) injection model. We found chronic CCl4 application to enhance ER stress and unfolded protein responses (UPR), including phosphorylation of eukaryotic initiation factor 2α
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Rogler, Charles E., Remon Bebawee, Joe Matarlo, et al. "Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver." Journal of Histochemistry & Cytochemistry 65, no. 1 (2016): 33–46. http://dx.doi.org/10.1369/0022155416675153.

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Recent investigations have reported many markers associated with human liver stem/progenitor cells, “oval cells,” and identified “niches” in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the
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Weerasinghe, Sujith V. W., You-Jin Jang, Robert J. Fontana, and M. Bishr Omary. "Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury." American Journal of Physiology-Gastrointestinal and Liver Physiology 307, no. 3 (2014): G355—G364. http://dx.doi.org/10.1152/ajpgi.00303.2013.

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Several serum markers are used to assess hepatocyte damage, but they have limitations related to etiology specificity and prognostication. Identification of novel hepatocyte-specific biomarkers could provide important prognostic information and better pathogenesis classification. We tested the hypothesis that hepatocyte-selective biomarkers are released after subjecting isolated mouse hepatocytes to Fas-ligand-mediated apoptosis. Proteomic analysis of hepatocyte culture medium identified the mitochondrial matrix protein carbamoyl phosphate synthetase-1 (CPS1) among the most readily detected pr
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Jones, B. A., Y. P. Rao, R. T. Stravitz, and G. J. Gores. "Bile salt-induced apoptosis of hepatocytes involves activation of protein kinase C." American Journal of Physiology-Gastrointestinal and Liver Physiology 272, no. 5 (1997): G1109—G1115. http://dx.doi.org/10.1152/ajpgi.1997.272.5.g1109.

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Toxic bile salts induce hepatocyte apoptosis, a model relevant to liver injury during cholestasis. However, the signaling mechanisms culminating in bile salt-induced apoptosis remain unclear. Because protein kinase C (PKC) is activated by bile salts in hepatocytes and causes apoptosis in other cells, we tested the hypothesis that bile salt-induced hepatocyte apoptosis is mediated by PKC. The PKC inhibitors chelerythrine and Go-6976 reduced, whereas a PKC agonist, phorbol 12-myristate 13-acetate (PMA), increased glycochenodeoxycholate (GCDC)-induced hepatocyte apoptosis. Membrane-associated tot
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Anderson, K., R. Andrews, L. Yin, et al. "Cytotoxicity of xenobiotics and expression of glutathione-S-transferases in immortalised rat hepatocyte cell lines." Human & Experimental Toxicology 17, no. 3 (1998): 131–37. http://dx.doi.org/10.1177/096032719801700301.

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1 Immortalised rat hepatocyte cell lines are more sensitive to the cytotoxicity of 1-chloro-2,4-dinitroben-zene and ethacrynic acid than primary cultures of hepatocytes. 2 Class alpha glutathione S-transferases are not expressed in immortalised hepatocyte cell lines. Class pi glutathione S-transferase expression is elevated in the immortalised cell lines compared with freshly isolated hepatocytes, but it is not as high as in the HTC rat hepatoma cell line. 3 Immortalised hepatocyte cell lines may provide a sensitive model system for detecting cytotoxicity associated with xenobiotics which are
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Chouhan, Manil, Juliana Puppi, Estela Solanas, Ragai R. Mitry, Anil Dhawan, and Robin D. Hughes. "Hepatocyte Labeling with 99mTc-GSA: A Potential Non-Invasive Technique for Tracking Cell Transplantation." International Journal of Artificial Organs 35, no. 6 (2012): 450–57. http://dx.doi.org/10.5301/ijao.5000096.

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Background: Hepatocyte transplantation is a promising alternative to orthotopic liver transplantation, however, the fate of transplanted hepatocytes is not well defined. 99mTc-galactosyl-serum albumin (99mTc-GSA) is a clinical scintigraphic agent which is specifically taken up by the hepatocyte asialoglycoprotein receptor (ASGPR). Aims: To investigate labeling of fresh and cryopreserved human hepatocytes and fresh rat hepatocytes in vitro using 99mTc-GSA Methods: Human and rat hepatocytes were isolated from liver tissue by collagenase perfusion. The ASGPR were characterized using immunohistoch
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Voieikova, D., L. Stepanova, O. Savchuk, L. Ostapchenko, and M. Kondro. "Protein analysis of rat hepatocytes under conditions glutamate-induced obesity and its correction." Bulletin of Taras Shevchenko National University of Kyiv. Series: Biology 70, no. 2 (2015): 81–84. http://dx.doi.org/10.17721/1728_2748.2015.70.81-84.

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We had characterized low-, medium- and high-molecular protein fractions of hepatocytes under development of glutamate-induced obesity and correction of nanocrystalline cerium dioxide and pioglitazone. Protein fractions were separated by electrophoresis using a 10 % Laemmli SDS-PAGE sodium dodecyl sulfate. Protein hepatocytes change under glutamate-induced obesity: high-protein reduced, and low-protein increased. Changes in hepatocyte proteins are consistent with previously established changes in protein content of hepatocytes under the influence HCD rich in fats and carbohydrates. We had notic
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Ernst, Linda M., Nancy B. Spinner, David A. Piccoli, Joanne Mauger, and Pierre Russo. "Interlobular Bile Duct Loss in Pediatric Cholestatic Disease is Associated with Aberrant Cytokeratin 7 Expression by Hepatocytes." Pediatric and Developmental Pathology 10, no. 5 (2007): 383–90. http://dx.doi.org/10.2350/06-09-0171.1.

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The objective of this study was to determine whether aberrant hepatic expression of cytokeratin 7 (CK7) and/or other putative stem cell markers is seen in pediatric cholestatic diseases. Eighteen liver biopsies and 14 liver explants from pediatric patients with extrahepatic biliary atresia (EHBA), Alagille syndrome (AGS), primary sclerosing cholangitis (PSC), inborn errors of bile acid synthesis, and progressive familial intrahepatic cholestasis (PFIC) were examined along with 5 histologically normal control liver biopsies. Immumohistochemical stains (CK7, CD56, and OV6) were performed on para
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Okumura, Nobuaki, Tomohiko Koh, Yuichi Hasebe, Taiichiro Seki, and Toyohiko Ariga. "A Novel Function of Thrombin-activatable Fibrinolysis Inhibitor during Rat Liver Regeneration and in Growth-promoted Hepatocytes in Primary Culture." Journal of Biological Chemistry 284, no. 24 (2009): 16553–61. http://dx.doi.org/10.1074/jbc.m109.011452.

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Thrombin-activatable fibrinolysis inhibitor (TAFI) exhibits anti-fibrinolytic activity by removing C-terminal lysine residues from fibrin or plasminogen receptor proteins on the cellular surface, and plays an important role in the regulation of fibrinolysis. In this study, we examined the regulation of TAFI in hepatocytes during liver regeneration, and revealed its pivotal role in hepatocyte proliferation. In rat models, partial hepatectomy or carbon tetrachloride (CCl4)-induced acute liver injury suppressed the levels of plasma TAFI activity and hepatic TAFI mRNA, whereas this operation marke
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47

Hisaka, Toru, Bernard Lardeux, Thierry Lamireau, et al. "Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation." Thrombosis and Haemostasis 91, no. 03 (2004): 569–75. http://dx.doi.org/10.1160/th03-06-0358.

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SummaryTissue factor pathway inhibitor-2 (TFPI-2) is a recently described serine proteinase inhibitor. Human and murine TFPI-2 share about 50% homology. The aim of this study was to investigate the cellular localization of human and murine TFPI-2 in the liver and the regulation of their expression during acute inflammation. Northern blot, in situ hybridization and studies on isolated hepatocytes demonstrated a high-level expression of TFPI-2 in murine hepatocytes. On the other hand, very little TFPI-2 mRNA expression could be detected in human liver. Studies with isolated human liver cells sug
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Grant, M. H., S. J. Smith, and M. D. Burke. "Strain differences in the maintenance of cytochrome P-450 and mixed-function-oxidase activities in cultured rat hepatocytes Effect of prostaglandins." Biochemical Journal 239, no. 3 (1986): 785–88. http://dx.doi.org/10.1042/bj2390785.

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The mixed-function-oxidase (MFO) activities, ethoxyresorufin and pentoxyphenoxazone O-dealkylase, of cultured Hooded-Lister(HL)-rat hepatocytes declined rapidly during 72 h of culture, whereas in Sprague-Dawley(SD)-rat hepatocytes the MFO activities increased between 24 and 72 h in culture. Cytochrome P-450 content declined at the same rate in both HL- and SD-rat hepatocyte cultures. NADPH:cytochrome c reductase and NADH:cytochrome b5 reductase were more stable in SD- than in HL-rat hepatocyte cultures. 16,16-Dimethylprostaglandins E2 and F2 alpha improved the maintenance of cytochrome P-450 c
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Wu, Zhi-Tao, Dan Yao, Shu-Yi Ji, et al. "Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology." Cellular Physiology and Biochemistry 38, no. 5 (2016): 1815–30. http://dx.doi.org/10.1159/000443120.

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Background/Aims: To develop a suitable hepatocyte-like cell model that could be a substitute for primary hepatocytes with essential transporter expression and functions. Induced hepatocyte-like (iHep) cells directly reprogrammed from mice fibroblast cells were fully characterized. Methods: Naïve iHep cells were transfected with nuclear hepatocyte factor 4 alpha (Hnf4α) and treated with selected small molecules. Sandwich cultured configuration was applied. The mRNA and protein expression of transporters were determined by Real Time PCR and confocal. The functional transporters were estimated by
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Billiar, T. R., R. D. Curran, B. G. Harbrecht, et al. "Association between synthesis and release of cGMP and nitric oxide biosynthesis by hepatocytes." American Journal of Physiology-Cell Physiology 262, no. 4 (1992): C1077—C1082. http://dx.doi.org/10.1152/ajpcell.1992.262.4.c1077.

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Hepatocytes are known to synthesize nitric oxide (NO) from L-arginine via an inducible NO synthase. Studies were performed to determine the relationship between hepatocyte NO production and the stimulation of hepatocyte soluble guanylate cyclase. A combination of lipopolysaccharide (LPS), interferon-gamma, tumor necrosis factor, and interleukin-1 stimulates the biosynthesis of large quantities of nitrite and nitrate (NO2- + NO3-). Hepatocyte NO2- + NO3- production was associated with only small increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels but much greater incre
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