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Hepatic regeneration

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https://www.readbyqxmd.com/read/27913222/human-liver-regeneration-in-advanced-cirrhosis-is-organized-by-the-portal-tree
#1
Katalin Dezső, András Rókusz, Edina Bugyik, Armanda Szücs, András Szuák, Bence Dorogi, Mátyás Kiss, Ágnes Nemeskéri, Péter Nagy, Sándor Paku
BACKGROUND&AIMS: In advanced cirrhosis new hepatocytic nodules are generated by budding of ductules in areas of parenchymal extinction. However, the vascular alterations in the areas of parenchymal extinction, the blood supply and the structure of the new hepatocytic nodules have not been analyzed in detail. METHODS: Explanted human cirrhotic livers of three different etiologies and two experimental models of cirrhosis in rats were examined thoroughly. 3D reconstruction of the immunohistochemically stained serial sections and casting of human and experimental cirrhotic livers have been used to reveal the structural organization of the regenerative buds...
November 29, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#2
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27911878/y-box-binding-protein-1-promotes-hepatocellular-carcinomainitiating-cell-progression-and-tumorigenesis-via-wnt-%C3%AE-catenin-pathway
#3
Hsiao-Mei Chao, Hong-Xuan Huang, Po-Hsiang Chang, Kuo-Chang Tseng, Atsushi Miyajima, Edward Chern
Y-box binding protein-1 (YB-1) is a pleiotropic molecule that binds DNA to regulate genes on a transcriptional level in the nucleus and binds RNA to modulate gene translation in the cytoplasm. In our previous studies, YB-1 was also characterized as a fetal hepatic protein that regulates the maturation of hepatocytes and is upregulated during liver regeneration. Moreover, YB-1 has been shown to be expressed in human hepatocellular carcinoma (HCC). However, the role of YB-1 in HCC remains unclear. Here, we aimed to characterize the role of YB-1 in HCC...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910729/identification-of-cytochrome-p450s-involved-in-the-metabolism-of-6-benzyl-1-benzyloxymethyl-5-iodouracil-w-1-using-human-recombinant-enzymes-and-rat-liver-microsomes-in-vitro
#4
Ying-Yuan Lu, Hai-Xu Cheng, Xin Wang, Xiao-Wei Wang, Jun-Yi Liu, Pu Li, Ya-Qing Lou, Jun Li, Chuang Lu, Guo-Liang Zhang
1. The aim of this study was to identify the hepatic metabolic enzymes, which involved in the biotransformation of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor (NNRTIs) in rat and human in vitro. 2. The parent drug of W-1 was incubated with RLMs or recombinant CYPs (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, respectively) in the presence or absence of NADPH regenerating system. The metabolites of W-1 were analyzed with liquid chromatography-ion trap-time of flight-mass spectrometry (LC-IT-TOF-MS)...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27907201/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-promotes-hepatic-stellate-cells-migration-via-canonical-nf-%C3%AE%C2%BAb-mmp9-pathway
#5
Mingcui Xu, Feng Zhang, Aixiu Wang, Chen Wang, Yu Cao, Ming Zhang, Mingming Zhang, Min Su, Xiaoping Zou, Guifang Xu, Yuzheng Zhuge
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65...
2016: PloS One
https://www.readbyqxmd.com/read/27904037/analysis-of-cyp2r1-and-cyp26a1-expression-patterns-in-regeneration-in-mice-with-liver-injury
#6
Akiyo Hirose, Wataru Ochiai, Yuka Yamamoto, Masashi Fukaya, Hiroshi Iwasaki, Nozomi Wakui, Ayumi Takahashi, Yusuke Takahashi, Satoshi Kitaoka, Jo Hatogai, Nobutomo Ikarashi, Kiyoshi Sugiyama
Cytochrome P450 enzymes (CYPs) are involved in the metabolism of various substances in the liver and small intestine and show markedly higher expression levels in the liver compared to other organs. The liver exhibits a remarkable capacity to regenerate. After excision of 70% of the liver, the organ can regenerate to its original size in approximately 1 week. Unlike the normal liver, in the injured liver, hepatic stem cells known as oval cells are considered to play an important role in regeneration. However, the role of CYPs in liver regeneration remains unclear...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903585/autophagy-in-chronic-liver-diseases-the-two-faces-of-janus
#7
Philippe Gual, Helene Gilgenkrantz, Sophie Lotersztajn
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis, steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (Macroautophagy and Chaperome-mediated autophagy) and chronic liver diseases have been reported...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903529/angiocrine-bmp2-signaling-in-murine-liver-controls-normal-iron-homeostasis
#8
Philipp-Sebastian Koch, Victor Olsavszky, Friederike Ulbrich, Carsten Sticht, Alexandra Demory, Thomas Leibing, Thomas Henzler, Mathias Meyer, Johanna Zierow, Sven Schneider, Katja Breitkopf-Heinlein, Haristi Gaitantzi, Bradley Spencer-Dene, Bernd Arnold, Kay Klapproth, Kai Schledzewski, Sergij Goerdt, Cyrill Géraud
Microvascular endothelial cells (EC) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific EC control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal EC (LSEC) are uniquely differentiated to fulfil important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSEC. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSEC using EC subtype-specific Stab2-Cre mice...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27894918/laser-speckle-contrast-imaging-and-oxygen-to-see-for-assessing-microcirculatory-liver-blood-flow-changes-following-different-volumes-of-hepatectomy
#9
Chong Hui Li, Xin Lan Ge, Ke Pan, Peng Fei Wang, Yi Nan Su, Ai Qun Zhang
OBJECTIVE: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. This study was designed to monitor and characterize the hepatic microcirculatory perfusion following different volumes of hepatectomy in rats by using laser speckle contrast image (LSCI) and Oxygen to See (O2C), a spectrometric device. METHODS: The microcirculatory liver blood flow of the rats that underwent 68%, 85% and 90% hepatectomy (68PH, 85PH and 90PH) was monitored with LSCI and O2C before and following the hepatectomy...
November 25, 2016: Microvascular Research
https://www.readbyqxmd.com/read/27880981/a-novel-glucagon-like-peptide-1-glucagon-receptor-dual-agonist-improves-steatohepatitis-and-liver-regeneration-in-mice
#10
M Pilar Valdecantos, Virginia Pardo, Laura Ruiz, Luis Castro-Sánchez, Borja Lanzón, Elisa Fernández-Millán, Carmelo García-Monzón, Ana I Arroba, Águeda González-Rodríguez, Fernando Escrivá, Álvarez Carmen, Francisco J Rupérez, Coral Barbas, Anish Konkar, Jacqui Naylor, David Hornigold, Ana Dos Santos, Maria Bednarek, Joseph Grimsby, Cristina M Rondinone, Ángela M Valverde
BACKGROUND AND AIMS: Since non-alcoholic steatohepatitis (NASH) is associated with impaired liver regeneration, we investigated the effects of G49, a dual glucagon-like peptide-1(GLP-1)/glucagon (GCG) receptor agonist, on NASH and hepatic regeneration. METHODS: C57Bl/6 mice fed chow or methionine and choline-deficient (MCD) diet for one week were divided into 4 groups: C (chow diet), MCD (MCD diet), C+G49 (chow diet plus G49) and M+G49 (MCD diet plus G49). Mice fed high fat diet (HFD) for 10 weeks were divided in groups: HFD and H+G49 (HFD plus G49)...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#11
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27862115/pediatric-acute-liver-failure-of-undetermined-cause-a-research-workshop
#12
Estella M Alonso, Simon P Horslen, Edward M Behrens, Edward Doo
: Pediatric Acute liver failure (PALF) is a potentially devastating condition which occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials...
November 14, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27861381/liver-graft-hyperperfusion-in-the-early-postoperative-period-promotes-hepatic-regeneration-2-weeks-after-living-donor-liver-transplantation-a-prospective-observational-cohort-study
#13
Sung Hye Byun, Hae Soo Yang, Jong Hae Kim
Hepatic regeneration is essential to meet the metabolic demands of partial liver grafts following living donor liver transplantation (LDLT). Hepatic regeneration is promoted by portal hyperperfusion of partial grafts, which produces shear stress on the sinusoidal endothelium. Hepatic regeneration is difficult to assess within the first 2 weeks after LDLT as the size of liver graft could be overestimated in the presence of postsurgical graft edema. In this study, we evaluated the effects of graft hyperperfusion on the rate of hepatic regeneration 2 weeks after LDLT by measuring hepatic hemodynamic parameters...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27860372/biomaterials-and-culture-technologies-for-regenerative-therapy-of-liver-tissue
#14
Roman A Perez, Cho-Rok Jung, Hae-Won Kim
Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions...
November 18, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27859840/value-of-mr-elastography-for-the-preoperative-estimation-of-liver-regeneration-capacity-in-patients-with-hepatocellular-carcinoma
#15
Siwon Jang, Jeong Min Lee, Dong Ho Lee, Ijin Joo, Jeong Hee Yoon, Won Chang, Joon Koo Han
PURPOSE: To demonstrate the negative relationship between liver stiffness (LS) values measured at preoperative magnetic resonance elastography (MRE) and the regeneration capacity of the remnant liver after major hepatectomy, in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-eight patients with HCC (mean age, 57.1) who had undergone liver computed tomography (CT) and 1.5T MRE prior to right hepatectomy were included in this retrospective study...
November 16, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27855391/suppression-of-microrna-219-5p-activates-keratinocyte-growth-factor-to-mitigate-severity-of-experimental-cirrhosis
#16
Li Chen, Xiang Cui, Peng Li, Cong Feng, Lili Wang, Hao Wang, Xuan Zhou, Bo Yang, Faqin Lv, Tanshi Li
BACKGROUND/AIMS: Keratinocyte growth factor (KGF) plays a critical role in prevention of cirrhosis and enhancement of liver regeneration. However, the molecular regulation of KGF in liver is unknown. MicroRNAs (miRNAs) control the pathogenesis of cirrhosis, whereas the exact involved miRNAs and molecular signaling pathways remain ill-defined. Here we addressed these questions. METHODS: We examined the correlation of the levels of miR-219-5p and KGF in the liver biopsies from patients with liver diseases...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27832649/bile-acids-and-the-potential-role-in-primary-biliary-cirrhosis
#17
Hang Yang, Zhijun Duan
BACKGROUND: Bile acids (BAs) play a potential role in regulating the whole-body metabolic homeostasis via the interaction with gut microbiome and the signal transduction as messengers, which establish a link between the primary biliary cirrhosis (PBC) and gut microbiome in many aspects, particularly with regard to the immune system of the body. PBC, as a chronic cholestatic liver disease characterised by the destruction of small intrahepatic bile ducts, causes fibrosis and potential cirrhosis without efficient therapies...
November 11, 2016: Digestion
https://www.readbyqxmd.com/read/27830546/thy-1-cd90-positive-hepatic-progenitor-cells-hepatoctyes-and-non-parenchymal-liver-cells-isolated-from-human-livers
#18
Thomas S Weiss, Rania Dayoub
In response to liver injury, hepatic cells, especially hepatocytes, can rapidly proliferate to repair liver damage. Additionally, it was shown that under certain circumstances liver resident cells with progenitor capabilities are involved in liver cell proliferation and differentiation. These hepatic progenitor cells (HPCs), known as oval cells in rodents, are derived from the canals of Hering, which are located in the periportal region of the liver. Regarding to different cell niches, which were defined for human HPCs, several markers have been used to identify these cells such as CD34, c-kit, OV-6, and Thy-1 (CD90)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#19
Michaël Maes, Mitchell R McGill, Tereza Cristina da Silva, Chloé Abels, Margitta Lebofsky, James L Weemhoff, Taynã Tiburcio, Isabel Veloso Alves Pereira, Joost Willebrords, Sara Crespo Yanguas, Anwar Farhood, Alain Beschin, Jo A Van Ginderachter, Silvia Penuela, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity...
November 8, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27805290/in-vitro-differentiated-hepatic-oval-like-cells-enhance-hepatic-regeneration-in-ccl4-induced-hepatic-injury
#20
Sana Javaid Awan, Maria Tayyab Baig, Faiza Yaqub, Asima Tayyeb, Gibran Ali
Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP(+) mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes...
November 2, 2016: Cell Biology International
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