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hepatocyte differentiation

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https://www.readbyqxmd.com/read/27916538/myofibroblasts-derived-from-hepatic-progenitor-cells-create-the-tumor-microenvironment
#1
Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki
Hepatic progenitor cells (HPCs) appear in response to several types of chronic injury in the human and rodent liver that often develop into liver fibrosis, cirrhosis, and primary liver cancers. However, the contribution of HPCs to the pathogenesis and progression of such liver diseases remains controversial. HPCs are generally defined as cells that can differentiate into hepatocytes and cholangiocytes. In this study, however, we found that HPCs isolated from the chronically injured liver can also give rise to myofibroblasts as a third type of descendant...
November 26, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27916074/-clinical-values-of-wnt3a-as-a-novel-biomarker-in-diagnosis-and-prognosis-of-hepatocellular-carcinoma
#2
L Wang, L H Pan, M Yao, W J Zheng, M Fang, L W Qiu, Z Z Dong, D F Yao
Objective: To explore Wnt3a expression in HCC tissues and serum, and to discuss its clinical diagnostic and prognostic value. Methods: The Wnt3a expressions were detected in a total of 186 patients (HCC, liver cirrhosis and chronic Hepatitis) and 40 controls by Elisa, comparing with AFP to evaluate its clinical diagnosis value. Wnt3a expressions in 80 HCC and surrounding tissues were analyzed by IHC, to explore its prognostic value. Results: Wnt3a with brown staining was mainly distributed in cytosol and of hepatocyte membrane...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27915491/the-effects-of-changes-in-glutathione-levels-through-exogenous-agents-on-intracellular-cysteine-content-and-protein-adduct-formation-in-chronic-alcohol-treated-vl17a-cells
#3
Mathan Kumar S, Madhumitha Haridoss, Kavitha Swaminathan, Ramesh Kumar G, Dahn L Clemens, Aparajita Dey
Alcohol mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N- acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed...
December 4, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27913249/comparison-of-the-transcriptomic-profile-of-hepatic-human-induced-pluripotent-stem-like-cells-cultured-in-plates-and-in-a-3d-microscale-dynamic-environment
#4
Eric Leclerc, Keiichi Kimura, Marie Shinohara, Mathieu Danoy, Morgane Le Gall, Taketomo Kido, Atsushi Miyajima, Teruo Fujii, Yasuyuki Sakai
We have compared the transcriptomic profiles of human induced pluripotent stem cells after their differentiation in hepatocytes like cells in plates and microfluidic biochips. The biochips provided a 3D and dynamic support during the cell differentiation when compared to the 2D static cultures in plates. The microarray have demonstrated the up regulation of important pathway related to liver development and maturation during the culture in biochips. Furthermore, the results of the transcriptomic profile, coupled with immunostaining, and RTqPCR analysis have shown typical biomarkers illustrating the presence of responders of biliary like cells, hepatocytes like cells, and endothelial like cells...
November 29, 2016: Genomics
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#5
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 2, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#6
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#7
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Sarka Lhotak, Pei Yu, Gabriel Gyulay, Guillaume Pare, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER localized transcription factor that directly upregulates sterol-regulatory genes, including PCSK9. Given that PCSK9 contributes to atherosclerosis by targeting low-density lipoprotein (LDL) receptor (LDLR) degradation, our present study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906439/in-vitro-neural-differentiation-of-bone-marrow-stromal-cells-induced-by-hepatocyte-growth-factor-and-glial-cell-derived-neurotrophic-factor
#8
Q Ma, M Cai, J-W Shang, J Yang, X-Y Gu, W-B Liu, Q Yang
OBJECTIVE: Bone marrow stromal cells (BMSCs) have great potential for cell-based transplantation therapy in treating neurological disease. However, the best combination of various trophic factors to produce full neural differentiation of BMSCs was still unclear. In our study, we aimed to investigate the neural differentiation capacity of rat BMSCs induced by growth factors including hepatocyte growth factor (HGF) and glial cell-derived neurotrophic factor (GDNF). MATERIALS AND METHODS:   Cell counting kit-8 (CCK-8) assay, BrdU cell proliferation assay and flow cytometry were implemented to evaluate whether GDNF and HGF had positive effects on the proliferation of BMSCs...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27904043/role-of-the-drug-metabolizing-enzyme-cyp-during-mouse-liver-development
#9
Wataru Ochiai, Akiyo Hirose, Taisuke Kawamura, Kyoko Komachi, Yuka Yamamoto, Satoshi Kitaoka, Jo Hatogai, Yoshiki Kusunoki, Risako Kon, Nobutomo Ikarashi, Kiyoshi Sugiyama
The drug-metabolizing enzyme CYP is mainly involved in the metabolism of various substances in the liver, such as drugs, endogenous substances, and carcinogens. Recent reports have also revealed that CYP1B1 plays a major role in the developmental process. Because the level of CYP expression is markedly high in the liver, we hypothesize that CYP plays a role in the developmental process of the liver. To verify this hypothesis, we analyzed the expression patterns of various CYP molecular species and their functions during the differentiation of embryonic stem cells (ES cells) into hepatocytes and the developmental process in mice...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903581/the-plasma-membrane-metal-ion-transporter-zip14-contributes-to-non-transferrin-bound-iron-uptake-by-human-%C3%AE-cells
#10
Richard Coffey, Mitchell D Knutson
The relationship between iron and β cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZIP14, ZIP8, and DMT1 to iron uptake by human β cells...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903234/acute-phase-proteins-and-their-potential-role-as-an-indicator-for-fish-health-and-in-diagnosis-of-fish-diseases
#11
Suvra Roy, Vikash Kumar, Vikas Kumar, B K Behera
The acute phase proteins are biochemically and functionally unrelated protein predominantly synthesized in the liver. The local inflammatory cells i.e. macrophages and neutrophils secretes various cytokines like IL-1, IL-6, IL-8 (interleukins) and TNF-α into bloodstream in response to injury and tissue damage, which stimulate hepatocytes to produce protein and release them into the circulation; these proteins are called as acute phase protein (e.g. C-reactive protein (CRP), serum amyloid A (SAA), metal binding protein, lysozyme, lectin, etc...
November 21, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#12
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27902686/genomic-characterization-of-metformin-hepatic-response
#13
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27902355/the-use-of-human-umbilical-cord-blood-serum-is-beneficial-for-the-continuous-production-of-hepatitis-c-virus
#14
Xiao-Yang Jiao, Rineke H G Steenbergen, D Lorne Tyrrell
In this study we investigated if human umbilical cord blood serum (CBS) is a suitable replacement for fetal bovine serum (FBS) in cultures of human hepatoma cell line Huh7.5, particularly regarding its capacity to maintain high growth rates, differentiation status and its ability to support robust HCV infection. Generally, CBS cultured Huh7.5 cells remained comparable to FBS cultured cells, and proliferated equally well. Albumin secretion, a hepatocyte differentiation marker, had increased 8x in CBS, however, most other hepatocyte markers we tested had not changed...
October 24, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27899483/integrin-linked-kinase-is-necessary-for-the-development-of-diet-induced-hepatic-insulin-resistance
#15
Ashley S Williams, Elijah Trefts, Louise Lantier, Carrie Grueter, Deanna P Bracy, Freyja D James, Ambra Pozzi, Roy Zent, David H Wasserman
The liver extracellular matrix (ECM) expands with high fat (HF) feeding. This finding led us to address whether receptors for the ECM, integrins, are key to the development of diet-induced hepatic insulin resistance. Integrin-linked kinase (ILK) is a downstream integrin signaling molecule involved in multiple hepatic processes including those related to differentiation, wound healing and metabolism. We tested the hypothesis that deletion of ILK in mice on a HF diet would disrupt the ECM-Integrin signaling axis thereby preventing the transformation into the insulin resistant liver...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899417/emerging-roles-of-glis3-in-neonatal-diabetes-type-1-and-type-2-diabetes
#16
Xianjie Wen, Yisheng Yang
GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid, and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism, and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations...
November 29, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27897167/ecm-proteins-in-a-microporous-scaffold-influence-hepatocyte-morphology-function-and-gene-expression
#17
Yan Wang, Myung Hee Kim, Hitomi Shirahama, Jae Ho Lee, Soon Seng Ng, Jeffrey S Glenn, Nam-Joon Cho
It is well known that a three-dimensional (3D) culture environment and the presence of extracellular matrix (ECM) proteins facilitate hepatocyte viability and maintenance of the liver-specific phenotype in vitro. However, it is not clear whether specific ECM components such as collagen or fibronectin differentially regulate such processes, especially in 3D scaffolds. In this study, a series of ECM-functionalized inverted colloidal crystal (ICC) microporous scaffolds were fabricated and their influence on Huh-7...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889947/pathological-findings-of-nash-and-nafld
#18
Kathryn Effendi, Kenichi Harada, Etsuko Hashimoto, Masayoshi Kage, Kazuhiko Koike, Fukuo Kondo, Masayuki Nakano, Hidenori Ojima, Takeshi Okanoue, Michiie Sakamoto, Yoshio Sumida, Hanako Tsujikawa, Gotaro Yamada, Yoh Zen
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver disease worldwide. NAFLD comprises a variety of clinical and histopathological changes that can be broadly divided into nonalcoholic fatty liver (NAFL, simple steatosis) and nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFL and NASH is important because NASH is a more advanced form. This diagnosis therefore determines the prognosis and therapeutic management. At present the interpretation of NASH is made based on the histopathological features of steatohepatitis, i...
November 27, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27885867/protein-corona-modulation-of-hepatocyte-uptake-and-molecular-mechanisms-of-gold-nanoparticle-toxicity
#19
Kyoungju Choi, Jim E Riviere, Nancy A Monteiro-Riviere
Protein corona formation over gold nanoparticles (AuNP) can modulate cellular responses by altering AuNP physicochemical properties. The liver plays an essential role in metabolism, detoxification and elimination of xenobiotics and drugs as well as circulating NP clearance. We investigated human hepatic uptake of 40 and 80nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas. AuNP-mediated cytotoxicity, reactive oxygen/reactive nitrogen species (ROS/RNS), and CYP activity in human hepatocytes as well as molecular mechanisms with 40nm bare and HP BPEI-AuNP were investigated...
November 25, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27881473/clinicopathological-features-of-neoplasms-with-neuroendocrine-differentiation-occurring-in-the-liver
#20
Yoriko Nomura, Osamu Nakashima, Jun Akiba, Sachiko Ogasawara, Shogo Fukutomi, Rin Yamaguchi, Hironori Kusano, Masayoshi Kage, Koji Okuda, Hirohisa Yano
BACKGROUND/AIMS: We investigated the clinicopathological features of hepatic neuroendocrine tumours (NET) and neuroendocrine carcinoma (NEC), which remain largely unknown. MATERIAL AND METHODS: We examined 1235 tumours from 1048 patients who had undergone curative hepatectomy for liver neoplasms at Kurume University Hospital. Pathological diagnoses were based on the 2010 WHO Classification of Tumours of the Digestive System. We performed immunostaining for hepatocyte markers (eg, hepatocyte paraffin (HepPar)-1), neuroendocrine markers (eg, chromogranin A (CGA)) and the proliferation marker (Ki-67)...
November 23, 2016: Journal of Clinical Pathology
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