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Gene Expression

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https://www.readbyqxmd.com/read/29973305/heat-stress-and-thermal-ablation-induce-local-expression-of-nerve-growth-factor-inducible-vgf-in-hepatocytes-and-hepatocellular-carcinoma-pre-clinical-and-clinical-studies
#1
Scott M Thompson, Danielle E Jondal, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
> Purpose: To test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Materials and Methods: Hepatocytes and HCC cells were subjected to moderate(45°C) or physiologic(37°C) heat stress for 10 minutes and assessed for VGF expression at 0-72 hours post-heat stress(N≥3 experiments). Orthotopic N1S1 HCC bearing rats were randomized to sham or laser-thermal ablation (3 wattsx90s) and liver/serum were harvested at 0-7 days postablation for analysis of VGF expression(N≥6 per group)...
July 4, 2018: Gene Expression
https://www.readbyqxmd.com/read/29929573/hepatic-gene-expression-during-the-perinatal-transition-in-the-rat
#2
Edward Hurley, Valerie Zabala, Joan M Boylan, Philip A Gruppuso, Jennifer A Sanders
During the immediate postnatal period, the liver, with its role in energy metabolism and macromolecule synthesis, playsa central role in the perinatal transition. Using RNA microarrays and several complementary computational analyses, we characterized changes in hepatic gene expression in the rat across a developmental period starting with the late gestation fetus (embryonic day 21), and including 30 min postnatal (PN), 4 hr PN, 12 hr PN, 1 day PN and 1 week after birth. Following subtle changes in gene expression at the earliest postnatal time point, there were marked changes that occurred between 4 hr and 12 hr after birth...
June 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29895352/direct-comparison-of-the-thioacetamide-and-azoxymethane-models-of-type-a-hepatic-encephalopathy-in-mice
#3
Stephanie Grant, Matthew McMillin, Gabriel Frampton, Anca D Petrescu, Elaina Williams, Victoria Jaeger, Jessica Kain, Sharon DeMorrow
Acute liver failure is a devastating consequence of hepatotoxic liver injury that can lead to the development of hepatic encephalopathy. There is no consensus on the best model to represent these syndromes in mice and therefore the aim of this study was to classify hepatic and neurological consequences of azoxymethane- and thioacetamide-induced liver injury. Azoxymethane-treated mice were euthanized at time points representing absence of, minor and significant stages of neurological decline. Thioacetamidetreated mice had tissue collected at up to 3 days following daily injections...
June 12, 2018: Gene Expression
https://www.readbyqxmd.com/read/29871716/hnf4%C3%AE-regulates-csad-to-couple-hepatic-taurine-production-to-bile-acid-synthesis-in-mice
#4
Yifeng Wang, David Matye, Nga Nguyen, Yuxia Zhang, Tiangang Li
BACKGROUND: cysteine dioxygenase 1 (CDO1) converts cysteine to cysteine sulfinic acid, which can be further converted by cysteine sulfinic acid decarboxylase (CSAD) to hypotaurine for taurine production. This cysteine catabolic pathway plays a major role in regulating hepatic cysteine homeostasis. Furthermore, taurine is used for bile acid conjugation, which enhances bile acid solubility and physiological function in the gut. Recent studies show that this cysteine catabolic pathway is repressed by bile acid signaling, but the molecular mechanisms have not been fully elucidated...
June 5, 2018: Gene Expression
https://www.readbyqxmd.com/read/29690953/stat3-regulates-liver-progenitor-cell-driven-liver-regeneration-in-zebrafish
#5
Mehwish Khaliq, Sungjin Ko, Yinzi Liu, Hualin Wang, Yonghua Sun, Lila Solnica-Kreze, Donghun Shin
After liver injury, regeneration manifests as either (1) hepatocytes proliferating to restore the lost hepatocyte massor (2) if hepatocyte proliferation is compromised, biliary epithelial cells (BECs) dedifferentiating into liver progenitor cells (LPCs), which subsequently differentiate into hepatocytes. Following pharmacogenetic ablation of hepatocytes in Tg(fabp10a:CFP-NTR) zebrafish, resulting in severe liver injury, signal transducer and activator of transcription 3 (Stat3) and its target gene and negative regulator, socs3a , were upregulated in regenerating livers...
April 24, 2018: Gene Expression
https://www.readbyqxmd.com/read/29540258/dna-damage-response-regulates-initiation-of-liver-regeneration-following-acetaminophen-overdose
#6
Prachi Borude, Bharat Bhushan, Udayan Apte
Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) with limited treatment options. It is known that liver regeneration following APAP-induced ALF is a deciding factor in the final outcome. Previous studies from our laboratory using an incremental dose model involving a regenerating (300 mg/kg, APAP300) and a nonregenerating (600 mg/kg, APAP600) dose of APAP in mice have revealed several proregenerative pathways that regulate regeneration after APAP overdose. Here we report that DNA damage and repair mechanisms regulate initiation of liver regeneration following APAP overdose...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29463347/deciphering-the-spectrum-of-mitochondrial-dna-mutations-in-hepatocellular-carcinoma-using-high-throughput-sequencing
#7
Chang Yu, Xuefeng Wang, Lifeng Huang, Ying Tong, Lili Chen, Hailong Wu, Qiang Xia, Xiaoni Kong
Accumulation of mitochondrial DNA (mtDNA) mutations has been proposed to contribute to the initiation and progression of tumors. By using high-throughput sequencing strategies, we measured 33 specimens including 11 hepatocellular carcinoma (HCC) tissues, 11 corresponding adjacent tissues, and 11 normal liver tissues. We identified 194 single nucleotide variants (SNVs; including insert and deletion) in 33 liver tissues, and 13 somatic novel mutations were detected, including 7 mutations in the coding region...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29409568/the-effect-of-selective-c-met-inhibitor-on-hepatocellular-carcinoma-in-the-met-active-%C3%AE-catenin-mutated-mouse-model
#8
Na Zhan, Adeola Adebayo Michael, Kaiyuan Wu, Gang Zeng, Aaron Bell, Junyan Tao, Satdarshan P Monga
Simultaneous mutations in CTNNB1 and activation of c-MET occur in 9%-12.5% of patients with hepatocellular carcinoma (HCC). Coexpression of c-MET-V5 and mutant β-catenin-Myc in mouse liver by sleeping beauty transposon/transposase and hydrodynamic tail vein injection (SB-HTVI) led to the development of HCC with 70% molecular identity to the clinical subset. Using this model, we investigated the effect of EMD1214063, a highly selective c-MET inhibitor. Five weeks after SB-HTVI when tumors were established, EMD1214063 (10 mg/kg) was administered by gastric gavage as a single agent on 5-day-on/3-day-off schedule, compared to vehicle only control...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29325602/bile-acid-metabolism-in-liver-pathobiology
#9
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29212576/the-effects-of-physical-exercise-on-fatty-liver-disease
#10
Dirk J van der Windt, Vikas Sud, Hongji Zhang, Allan Tsung, Hai Huang
The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29096734/endocrine-adiponectin-fgf15-19-axis-in-ethanol-induced-inflammation-and-alcoholic-liver-injury
#11
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver disease, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades, and exert similar beneficial functions...
May 18, 2018: Gene Expression
https://www.readbyqxmd.com/read/29580319/liver-and-pancreas-do-similar-embryonic-development-and-tissue-organization-lead-to-similar-mechanisms-of-tumorigenesis
#12
Elsa Ghurburrun, Ivan Borbath, Frédéric P Lemaigre, Patrick Jacquemin
Liver and pancreas are closely associated organs which share a common embryological origin. They display amphicrine properties and have similar exocrine organization with parenchymal cells, namely hepatocytes and acinar cells, secreting bile and pancreatic juice into the duodenum via a converging network of bile ducts and pancreatic ducts. Here we compare and highlight the similarities of molecular mechanisms leading to liver and pancreatic cancer development. We suggest that unraveling tumor development in an organ may provide insight into our understanding of carcinogenesis in the other organ...
March 26, 2018: Gene Expression
https://www.readbyqxmd.com/read/29580318/%C3%AE-7-nachr-knockout-mice-decreases-biliary-hyperplasia-and-liver-fibrosis-in-cholestatic-bile-duct-ligated-mice
#13
Laurent Ehrlich, April O'Brien, Chad Hall, Tori White, Lixian Chen, Nan Wu, Julie Venter, Marinda Scrushy, Muhammad Mubarak, Fanyin Meng, David Dostal, Chaodong Wu, Terry C Lairmore, Gianfranco Alpini, Shannon Glaser
α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. METHODS: Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition...
March 26, 2018: Gene Expression
https://www.readbyqxmd.com/read/29221500/analysis-of-naturally-occurring-resistance-associated-variants-to-ns3-4a-protein-inhibitors-ns5a-protein-inhibitors-and-ns5b-polymerase-inhibitors-in-patients-with-chronic-hepatitis-c
#14
Danhui Sun, Mingjia Dai, Shanshan Shen, Chunyang Li, Xuebing Yan
The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011, and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with HCV. HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for the treatment of HCV infection in combination with PEG-IFN-α/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugs...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29212575/oct4-is-crucial-for-transdifferentiation-of-hepatocytes-to-biliary-epithelial-cells-in-an-in-vitro-organoid-culture-model
#15
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, Harish S Parihar, Huy Nguyen, George K Michalopoulos, Vishakha S Bhave
Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, whether Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29096730/updates-on-dietary-models-of-nonalcoholic-fatty-liver-disease-current-studies-and-insights
#16
Kristen Stephenson, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Joanne Thomson, Gianfranco Alpini, Heather Francis
Nonalcoholic fatty liver disease (NAFLD) is a disease of increasing interest, as its prevalence is on the rise. NAFLD has been linked to metabolic syndrome, which is becoming more common due to the Western diet. Because NAFLD can lead to cirrhosis and related complications including hepatocellular carcinoma, the increasing prevalence is concerning, and medical therapy aimed at treating NAFLD is of great interest. Researchers studying the effects of medical therapy on NAFLD use dietary mouse models. The two main types of mouse model diets are the methionine- and choline-deficient (MCD) diet and the Western-like diet (WD)...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29070148/molecular-mechanisms-driving-cholangiocarcinoma-invasiveness-an-overview
#17
Simone Brivio, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco
The acquisition of invasive functions by tumor cells is a first and crucial step toward the development of metastasis, which nowadays represents the main cause of cancer-related death. Cholangiocarcinoma (CCA), a primary liver cancer originating from the biliary epithelium, typically develops intrahepatic or lymph node metastases at early stages, thus preventing the majority of patients from undergoing curative treatments, consistent with their very poor prognosis. As in most carcinomas, CCA cells gradually adopt a motile, mesenchymal-like phenotype, enabling them to cross the basement membrane, detach from the primary tumor, and invade the surrounding stroma...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#18
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the US, and decades of intense study of its pathogenesis resulted in the development of the antidote N-acetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for the development of additional therapeutic approaches that can benefit late-presenting patients...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/28893365/coffee-consumption-and-prevention-of-cirrhosis-in-support-of-the-caffeine-hypothesis
#19
Jonathan A Dranoff
Coffee is acknowledged as the most widely used drug worldwide. Coffee is also a foodstuff, so its use is often used to satisfy dietary urges. When used as a drug, coffee is normally consumed as a stimulant rather than to treat or prevent particular diseases. Recently, coffee consumption has been inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma. Experiments in cellular and animal models have provided biological plausibility for coffee as an antifibrotic agent in the liver...
March 21, 2018: Gene Expression
https://www.readbyqxmd.com/read/29519268/hepatocyte-wnts-are-dispensable-during-diethylnitrosamine-and-carbon-tetrachloride-induced-injury-and-hepatocellular-cancer
#20
Morgan Preziosi, Minakshi Poddar, Sucha Singh, Satdarshan P Monga
Activation of the Wnt/β-catenin signaling is reported in large subsets of hepatocellular carcinoma (HCC). Upregulationof Wnt genes is one contributing mechanism. In the current study, we sought to address the role of hepatocyte-derived Wnts in a model of hepatic injury, fibrosis and carcinogenesis. We subjected hepatocyte-specific Wntless knockout mice (HP-KO), unable to secrete Wnts from hepatocytes, and littermate controls (HP-CON), to diethylnitrosamine and carbon tetrachloride (DEN/CCl4) and harvested at 3, 5, and 6 months for histological and molecular analysis...
March 8, 2018: Gene Expression
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