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Gene Expression

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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
#1
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 Hepatitis C virus (HCV). HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for treatment of HCV infection in combination with PEG-IFNα/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 drugsOur research showed that natural resistance to HCV DAAs was found in treatment-naïve CHC patients and that the drug resistance mutation rates differ in various HCV genotypes...
December 8, 2017: Gene Expression
https://www.readbyqxmd.com/read/29212576/the-effects-of-physical-exercise-on-fatty-liver-disease
#2
Dirk J van der Windt, Vikas Sud, Hongji Zhang, Allan Tsung, Hai Huang
The increasing prevalence of obesity has made non-alcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form non-alcoholic 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...
December 6, 2017: 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
#3
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, Harish S Parihar, Huy Nguyen, George K Michalopoulos, Vishakha Bhave
BACKGROUND: 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, if Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. METHODS: We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation...
December 6, 2017: Gene Expression
https://www.readbyqxmd.com/read/29096734/endocrine-adiponectin-fgf15-19-axis-in-ethanol-induced-inflammation-and-alcoholic-liver-injury
#4
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver diseases, 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...
November 2, 2017: Gene Expression
https://www.readbyqxmd.com/read/29096730/updates-on-dietary-models-of-non-alcoholic-fatty-liver-disease-current-studies-and-insights
#5
Kristen Stephenson, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Joanne Thomson, Gianfranco Alpini, Heather Francis
Non-alcoholic 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. Since 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 cholinedeficient (MCD) diet and Western-like Diet (WD)...
November 2, 2017: Gene Expression
https://www.readbyqxmd.com/read/29070148/molecular-mechanisms-driving-cholangiocarcinoma-invasiveness-an-overview
#6
Simone Brivio, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco
The acquisition of invasive functions by tumor cells is a first and crucial step towards 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...
October 25, 2017: Gene Expression
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#7
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and decades of intense study of its pathogenesis resulted in development of the antidote Nacetylcysteine, 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 development of additional therapeutic approaches which can benefit late presenting patients...
October 20, 2017: Gene Expression
https://www.readbyqxmd.com/read/28915934/increased-yap-activation-is-associated-with-hepatic-cyst-epithelial-cell-proliferation-in-arpkd-chf
#8
Lu Jiang, Lina Sun, Genea Edwards, Michael Manley, Darren P Wallace, Seth Septer, Chirag Manohar, Michele T Pritchard, Udayan Apte
Autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF) is a rare but fatal genetic disease characterized by progressive cyst development in the kidneys and liver. Liver cysts arise from aberrantly proliferative cholangiocytes accompanied by pericystic fibrosis and inflammation. Yes associated protein (YAP), the downstream effector of the Hippo signaling pathway, is implicated in human hepatic malignancies such as hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma, but its role in hepatic cystogenesis in CHF/ARPKD is unknown...
September 15, 2017: Gene Expression
https://www.readbyqxmd.com/read/28893365/coffee-consumption-and-prevention-of-cirrhosis-in-support-of-the-caffeine-hypothesis
#9
Jonathan Dranoff
It is widely acknowledged that coffee is the most widely used drug on Earth. While this is true, coffee is also a foodstuff with wide variation, so its use is often directed at satisfying dietary urges. When used as a drug, coffee is almost invariably used as a stimulant rather than to treat or prevent particular diseases. Thus, it has been an exciting revelation in recent years that coffee consumption is inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma.As is often the case, epidemiological observations have preceded pathophysiological explanations for this effect...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28893353/the-cholangiocyte-adenosine-il6-axis-regulates-survival-during-biliary-cirrhosis
#10
Elise Lavoie, Michel Fausther, Jessica Goree, Jonathan Dranoff
BACKGROUND AND AIMSEpithelial response to injury is critical to the pathogenesis of biliary cirrhosis, and IL6 has been suggested as a mediator of this phenomenon. Several liver cell types can secrete IL6 following activation by various signaling molecules including circulating adenosine. The aims of this study are to assess whether adenosine can induce IL6 secretion by cholangiocytes via the A2b adenosine receptor (A2bAR) and determine the effect of A2bAR-sensitive IL6 release on injury response in biliary cirrhosis...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28893351/hepatic-ischemia-reperfusion-mechanisms-of-tissue-injury-repair-and-regeneration
#11
Takanori Konishi, Alex Lentsch
Hepatic ischemia reperfusion (I/R) injury is a major complication of liver surgery, including liver resection, liver transplantation, and trauma surgery. Much has been learned about the inflammatory injury response induced by I/R, including the cascade of proinflammatory mediators and recruitment of activated leukocytes. In this review, we discuss the complex network of events that culminate in liver injury after I/R, including cellular, protein, and molecular mechanisms. In addition we address the known endogenous regulatory mediators that function to maintain homeostasis and resolve injury...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28770701/cell-death-and-prognosis-of-mortality-in-alcoholic-hepatitis-patients-using-plasma-keratin-18
#12
Benjamin Woolbright, Brian Bridges, Winston Dunn, Jody Olson, Steven Weinman, Hartmut Jaeschke
Alcoholic liver disease encompasses the progressive stages of liver dysfunction that culminates in alcoholic cirrhosis(AC) and in severe cases alcoholic hepatitis (AH). Currently, prognostic scores have limited specificity and sensitivity. Plasma keratin-18 (K18) levels are elevated during liver disease and may be biomarkers of outcome. The objective of this study was to determine if total K18 (M65) or caspase-cleaved K18 (M30) levels were different between AC and AH patients. M65 and M30 levels were measured in plasma of consented healthy controls, and patients with AC and AH...
August 3, 2017: Gene Expression
https://www.readbyqxmd.com/read/28474571/role-and-regulation-of-p65-%C3%AE-catenin-association-during-liver-injury-and-regeneration-a-complex-relationship
#13
Kari Nejak-Bowen, Akshata Moghe, Pamela Cornuet, Morgan Preziosi, Shanmugam Nagarajan, Satdarshan P Monga
An important role for β-catenin in regulating p65 (a subunit of NF-κB) during acute liver injury has recently been elucidated through use of conditional β-catenin knockout mice, which show protection from apoptosis through increased activation of p65. Thus, we hypothesized that the p65/β-catenin complex may play a role in regulating processes such as cell proliferation during liver regeneration. We show through in vitro and in vivo studies that the p65/β-catenin complex is regulated through the TNF-α pathway and not through Wnt signaling...
July 7, 2017: Gene Expression
https://www.readbyqxmd.com/read/28411363/animal-models-of-alcoholic-liver-disease-pathogenesis-and-clinical-relevance
#14
Bin Gao, Ming-Jiang Xu, Adeline Bertola, Hua Wang, Zhou Zhou, Suthat Liangpunsakul
Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals...
July 7, 2017: Gene Expression
https://www.readbyqxmd.com/read/28251883/tomm22-knockdown-mediated-hepatocyte-damages-elicit-both-the-formation-of-hybrid-hepatocytes-and-biliary-conversion-to-hepatocytes-in-zebrafish-larvae
#15
Jianchen Wu, Tae-Young Choi, Donghun Shin
The liver has a highly regenerative capacity. In the normal liver, hepatocytes proliferate to restore lost liver mass. However, when hepatocyte proliferation is impaired, biliary epithelial cells (BECs) activate and contribute to hepatocytes. We previously reported in zebrafish that upon severe hepatocyte ablation, BECs extensively contribute to regenerated hepatocytes. It was also speculated that BEC-driven liver regeneration might occur in another zebrafish liver injury model in which temporary knockdown of the mitochondrial import gene tomm22 by morpholino antisense oligonucleotides (MO) induces hepatocyte death...
July 7, 2017: Gene Expression
https://www.readbyqxmd.com/read/28234577/c57bl-6-substrains-exhibit-different-responses-to-acute-carbon-tetrachloride-exposure-implications-for-work-involving-transgenic-mice
#16
Jennifer M McCracken, Prabhakar Chalise, Shawn M Briley, Katie L Dennis, Lu Jiang, Francesca E Duncan, Michele T Pritchard
Biological differences exist between strains of laboratory mice, and it is becoming increasingly evident that there are differences between substrains. In the C57BL/6 mouse, the primary substrains are called 6J and 6N. Previous studies have demonstrated that 6J and 6N mice differ in response to many experimental models of human disease. The aim of our study was to determine if differences exist between 6J and 6N mice in terms of their response to acute carbon tetrachloride (CCl4) exposure. Mice were given CCl4 once and were euthanized 12 to 96 h later...
July 7, 2017: Gene Expression
https://www.readbyqxmd.com/read/28635586/gc-1-a-thyromimetic-with-multiple-therapeutic-applications-in-liver-disease
#17
Amedeo Columbano, Grazia Chiellini, Marta Anna Kowalik
Thyroid hormones, namely 3,5,3'-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine (thyroxine or T4), influence a variety of physiological processes that have important implications in fetal development, metabolism, cell growth and proliferation. While THs elicit several beneficial effects on lipid metabolism and improve myocardial contractility, these therapeutically desirable effects are associated to a thyrotoxic state, that severely limits the possible use of THs as therapeutic agents. Therefore, several efforts have been made to develop T3 analogues that could retain the beneficial actions (triglyceride, cholesterol, obesity and body mass lowering), without the adverse TH-dependent side effects...
June 13, 2017: Gene Expression
https://www.readbyqxmd.com/read/28488569/gene-expression-in-the-liver-remnant-is-significantly-affected-by-the-size-of-partial-hepatectomy-an-experimental-rat-study
#18
Michelle Meier, Anders Riegels Knudsen, Kasper Jarlhelt Andersen, Niels Christian Bjerregaard, Uffe Birk Jensen, Frank Viborg Mortensen
Background Extended hepatectomies may result in post-hepatectomy liver failure, a conditionwith a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy.Methods 30 Wistar rats were subjected to 30%, 70%, or 90% partial hepatectomy, sham operation or no operation. 24 hours following resection liver tissue was harvested and genome wide expression analysis was performed.Results Cluster analysis revealed 2 main groupings, one containing the PH(90%) and one containing the remaining groups (baseline, sham, PH(30%) and PH(70%))...
May 9, 2017: Gene Expression
https://www.readbyqxmd.com/read/28485270/a-review-of-the-scaffold-protein-menin-and-its-role-in-hepatobiliary-pathology
#19
Laurent Ehrlich, Chad Hall, Fanyin Meng, Terry Lairmore, Gianfranco Alpini, Shannon Glaser
Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome with neuroendocrine tumorigenesis of the parathyroid glands, pituitary gland, and pancreatic islet cells. The MEN1 gene codes for the canonical tumor suppressor protein, menin. Its protein structure has recently been crystallized, and it has been investigated in a multitude of other tissues. In this review, we summarize recent advancements in understanding the structure of the menin protein and its function as a scaffold protein in histone modification and epigenetic gene regulation...
April 28, 2017: Gene Expression
https://www.readbyqxmd.com/read/28409553/the-thyromimetic-kb2115-eprotirome-induces-rat-hepatocyte-proliferation
#20
Marta Szydlowska, Monica Pibiri, Andrea Perra, Elisabetta Puliga, Sandra Mattu, Giovanna M Ledda-Columbano, Amedeo Columbano, Vera P Leoni
Although the hepatomitogenic activity of T3 is well established, the wide range of harmful effects exerted by this hormone precludes its use in regenerative therapy. The aim of this study was to investigate whether an agonist of TR, KB2115 (Eprotirome) could exert a mitogenic effect in the liver, without most of the adverse T3/TR-dependent side effects. F-344 rats treated with KB2115 for one week displayed a massive increase in bromodeoxyuridine incorporation (from 20 to 40% vs. 5% of controls), which was associated with increased mitotic activity in the absence of significant signs of liver toxicity...
April 13, 2017: Gene Expression
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