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https://www.readbyqxmd.com/read/28636885/differential-changes-in-the-pharmacokinetics-of-statins-in-collagen-induced-arthritis-rats
#1
Chun-Han Lin, Ke-Wei Hsu, Chia-Hao Chen, Yow-Shieng Uang, Chun-Jung Lin
The elevated systemic levels of cytokines in rheumatoid arthritis (RA) can change the expression of metabolic enzymes and transporters. Given that statins are lipid-lowering agents frequently used in RA patients with concurrent cardiovascular diseases, the objective of the present study was to investigate the impacts of RA on the pharmacokinetics of statins of different disposition properties in rats with collagen-induced arthritis (CIA). The expression of metabolic enzymes and transporters in tissues of CIA rats were analyzed by RT-qPCR...
June 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#2
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28627604/the-c-terminus-domain-of-the-hepatitis-b-virus-x-protein-stimulates-the-proliferation-of-mouse-foetal-hepatic-progenitor-cells-although-it-is-not-required-for-the-formation-of-spheroids
#3
Liming Yu, Shu Chen, Na Luo, Song He
The hepatitis B virus X (HBx) protein is an important factor in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). The C-terminal region of HBx plays a major role in the replication of HBV. Notably, HBx promotes the expansion and tumourigenesis of hepatic progenitor cells (HPCs) in mice. However, it remains unclear as to whether the C-terminal region of HBx is required for the stimulation fo the proliferation of mouse foetal HPCs (FHPCs). In our study, we used EpCAM+, CD133+ and CD49f+ FHPCs, which are bipotential clonogenic cells...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28625011/liver-epithelioid-progenitor-cells-derived-from-fetal-luxi-bovine-alleviate-liver-fibrosis
#4
Kunfu Wang, Hao Liu, Jinjuan Yang, Caiyun Ma, Zebiao Zhang, Dong Zheng, Weijun Guan
Liver epithelioid progenitor cells (LEPCs) have important roles in liver therapy because of their hepatic differentiation potency in vitro and in vivo. Despite many researches on humans, mice, and rats, equivalent progenitor cells derived from bovine are relatively rare. The purpose of our current study is to characterize bovine LEPCs, and research on the cure potency of this heteroplastic progenitor cells on mice liver fibrosis. We have used collagenase IV digesting and differential adhesion method to isolate slabstone shape, EpCAM, LGR5, NCAM1 and SOX9 positive progenitor cells from fetal Luxi bovine liver...
June 17, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28624798/selection-of-optimal-molecular-targets-for-tumor-specific-imaging-in-pancreatic-ductal-adenocarcinoma
#5
Willemieke Tummers, Arantza Farina Sarasqueta, Martin Boonstra, Hendrica Prevoo, Cornelis Sier, Sven Mieog, Johannes Morreau, Casper van Eijck, Peter Kuppen, Cornelis van de Velde, Bert Bonsing, Alexander Vahrmeijer, Rutger-Jan Swijnenburg
Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR)...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622294/hepatocyte-nuclear-factor-1b-is-a-novel-negative-regulator-of-white-adipocyte-differentiation
#6
Xin Wang, Hao Wu, Weihua Yu, Jiangzheng Liu, Jie Peng, Nai Liao, Jieling Zhang, Xiaodi Zhang, Chunxu Hai
Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28620383/ly6c-hi-monocytes-and-their-macrophage-descendants-regulate-neutrophil-function-and-clearance-in-acetaminophen-induced-liver-injury
#7
Nadine Graubardt, Milena Vugman, Odelia Mouhadeb, Gabriele Caliari, Metsada Pasmanik-Chor, Debby Reuveni, Ehud Zigmond, Eli Brazowski, Eyal David, Lousie Chappell-Maor, Steffen Jung, Chen Varol
Monocyte-derived macrophages (MoMF) play a pivotal role in the resolution of acetaminophen-induced liver injury (AILI). Timely termination of neutrophil activity and their clearance are essential for liver regeneration following injury. Here, we show that infiltrating Ly6C(hi) monocytes, their macrophage descendants, and neutrophils spatially and temporally overlap in the centrilobular necrotic areas during the necroinflammatory and resolution phases of AILI. At the necroinflammatory phase, inducible ablation of circulating Ly6C(hi) monocytes resulted in reduced numbers and fractions of reactive oxygen species (ROS)-producing neutrophils...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620221/mesenchymal-stem-cell-derived-exosomes-as-a-new-therapeutic-strategy-for-liver-diseases
#8
REVIEW
Guohua Lou, Zhi Chen, Min Zheng, Yanning Liu
The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28618926/diagnostic-relevance-of-a-novel-multiplex-immunoassay-panel-in-breast-cancer
#9
Natalie Hermann, Katja Dressen, Lars Schroeder, Manuel Debald, Frank A Schildberg, Gisela Walgenbach-Bruenagel, Karina Hettwer, Steffen Uhlig, Walther Kuhn, Gunther Hartmann, Stefan Holdenrieder
Multiple factors contribute to the development and progression of breast cancer. Markers of tumor growth and invasion, cell death, immune activation, and angiogenesis can be assessed in parallel by a novel multiplex immunoassay panel. The diagnostic performance of a multiplex cancer biomarker magnetic bead panel comprising 24 tumor associated parameters was evaluated in sera of 154 women including 77 patients with breast cancer, 10 with precancerous lesions, 31 with benign breast diseases, and 36 healthy controls...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28614297/multilineage-communication-regulates-human-liver-bud-development-from-pluripotency
#10
J Gray Camp, Keisuke Sekine, Tobias Gerber, Henry Loeffler-Wirth, Hans Binder, Malgorzata Gac, Sabina Kanton, Jorge Kageyama, Georg Damm, Daniel Seehofer, Lenka Belicova, Marc Bickle, Rico Barsacchi, Ryo Okuda, Emi Yoshizawa, Masaki Kimura, Hiroaki Ayabe, Hideki Taniguchi, Takanori Takebe, Barbara Treutlein
Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28609676/hepatocellular-differentiation-status-is-characterized-by-distinct-subnuclear-localization-and-form-of-the-chanzyme-trpm7
#11
Adenike Ogunrinde, Robyn D Pereira, Natalie Beaton, D Hung Lam, Christiane Whetstone, Ceredwyn E Hill
The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization. We used electrophysiological and immunofluorescence approaches to establish whether hepatocellular differentiation is associated with altered TRPM7 expression...
June 10, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28609656/kupffer-cell-derived-tnf-triggers-cholangiocellular-tumorigenesis-through-jnk-due-to-chronic-mitochondrial-dysfunction-and-ros
#12
Detian Yuan, Shan Huang, Emanuel Berger, Lei Liu, Nina Gross, Florian Heinzmann, Marc Ringelhan, Tracy O Connor, Mira Stadler, Michael Meister, Julia Weber, Rupert Öllinger, Nicole Simonavicius, Florian Reisinger, Daniel Hartmann, Rüdiger Meyer, Maria Reich, Marco Seehawer, Valentina Leone, Bastian Höchst, Dirk Wohlleber, Simone Jörs, Marco Prinz, Duncan Spalding, Ulrike Protzer, Tom Luedde, Luigi Terracciano, Matthias Matter, Thomas Longerich, Percy Knolle, Thomas Ried, Verena Keitel, Fabian Geisler, Kristian Unger, Einat Cinnamon, Eli Pikarsky, Norbert Hüser, Roger J Davis, Darjus F Tschaharganeh, Roland Rad, Achim Weber, Lars Zender, Dirk Haller, Mathias Heikenwalder
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28607606/diagnostic-value-of-gd-eob-dtpa-mri-for-hepatocellular-adenoma-a-meta-analysis
#13
Yongfei Guo, Wenjuan Li, Zhinan Xie, Yi Zhang, Yijie Fang, Wenli Cai, Guobin Hong
Objective: This study aimed to systematically review the gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) findings of hepatocellular adenoma (HCA), especially focusing on the diagnostic value of low signal intensity (SI) in the hepatocyte-phase (HBP) for differentiating HCA from focal nodular hyperplasia (FNH). Methods: A thorough literature search was conducted in PubMed, Excerpta Medica Database (EMBASE) and China National Knowledge Infrastructure databases (CNKI) to identify studies evaluating Gd-EOB-DTPA-MRI presentations of HCA...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28607595/e2f8-is-a-potential-therapeutic-target-for-hepatocellular-carcinoma
#14
REVIEW
Yi Lv, Jia Xiao, Jing Liu, Feiyue Xing
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28603487/the-onecut-transcription-factors-regulate-differentiation-and-distribution-of-dorsal-interneurons-during-spinal-cord-development
#15
Karolina U Kabayiza, Gauhar Masgutova, Audrey Harris, Vincent Rucchin, Benvenuto Jacob, Frédéric Clotman
During embryonic development, the dorsal spinal cord generates numerous interneuron populations eventually involved in motor circuits or in sensory networks that integrate and transmit sensory inputs from the periphery. The molecular mechanisms that regulate the specification of these multiple dorsal neuronal populations have been extensively characterized. In contrast, the factors that contribute to their diversification into smaller specialized subsets and those that control the specific distribution of each population in the developing spinal cord remain unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28603032/%C3%AE-2-adrenergic-receptor-mediated-in-vitro-regulation-of-human-hepatic-drug-transporter-expression-by-epinephrine
#16
Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP...
June 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28602994/fish-collagen-peptide-inhibits-the-adipogenic-differentiation-of-preadipocytes-and-ameliorates-obesity-in-high-fat-diet-fed-mice
#17
Eun Ji Lee, Jinwoo Hur, Sun Ah Ham, Yeonji Jo, SangYoon Lee, Mi-Jung Choi, Han Geuk Seo
Bioactivities of fish collagen peptide are now being elucidated in diverse biological systems. Here, we investigated the effect of fish collagen peptide on the adipogenic differentiation of 3T3-L1 preadipocytes and in obese mice fed a high fat diet (HFD). Subcritical water-hydrolyzed fish collagen peptide (SWFCP) significantly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes, which was accompanied by decreased expression of CCAAT-enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and adipocyte protein 2 (aP2) genes, key regulators of differentiation and maintenance of adipocytes...
June 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28602611/dna-methyltransferases-modulate-hepatogenic-lineage-plasticity-of%C3%A2-mesenchymal-stromal-cells
#18
Chien-Wei Lee, Wei-Chih Huang, Hsien-Da Huang, Yi-Hsiang Huang, Jennifer H Ho, Muh-Hwa Yang, Vincent W Yang, Oscar K Lee
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor β1 (TGFβ1), which in turn controls hepatogenic differentiation and de-differentiation...
June 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28600910/dried-human-skin-fibroblasts-as-a-new-substratum-for-functional-culture-of-hepatic-cells
#19
Agnieszka Wencel, Karolina Ewa Zakrzewska, Anna Samluk, Bartłomiej Henryk Noszczyk, Dorota Genowefa Pijanowska, Krzysztof Dariusz Pluta
The primary hepatocytes culture is still one of the main challenges in toxicology studies in the drug discovery process, development of in vitro models to study liver function, and cell-based therapies. Isolated hepatocytes display a rapid decline in viability and liver-specific functions including albumin production, conversion of ammonia to urea, and activity of the drug metabolizing enzymes. A number of methods have been developed in order to maintain hepatocytes in their highly differentiated state in vitro...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28599080/bmp-signaling-governs-biliary-driven-liver-regeneration-in-zebrafish-via-tbx2b-and-id2a
#20
Tae-Young Choi, Mehwish Khaliq, Shinya Tsurusaki, Nikolay Ninov, Didier Y R Stainier, Minoru Tanaka, Donghun Shin
Upon mild liver injury, new hepatocytes originate from pre-existing hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast-like cells (HB-LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration...
June 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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