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Gene Expression

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https://www.readbyqxmd.com/read/28770701/cell-death-and-prognosis-of-mortality-in-alcoholic-hepatitis-patients-using-plasma-keratin-18
#1
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/28635586/gc-1-a-thyromimetic-with-multiple-therapeutic-applications-in-liver-disease
#2
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/28411363/animal-models-of-alcoholic-liver-disease-pathogenesis-and-clinical-relevance
#3
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
#4
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
#5
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/28488569/gene-expression-in-the-liver-remnant-is-significantly-affected-by-the-size-of-partial-hepatectomy-an-experimental-rat-study
#6
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
#7
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/28474571/role-and-regulation-of-p65-%C3%AE-catenin-association-during-liver-injury-and-regeneration-a-complex-relationship
#8
Kari Nejak-Bowen, Akshata Moghe, Pamela Cornuet, Morgan Preziosi, Shanmugam Nagarajan, Satdarshan Ps 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- pathway, and not through Wnt signaling...
April 28, 2017: Gene Expression
https://www.readbyqxmd.com/read/28409553/the-thyromimetic-kb2115-eprotirome-induces-rat-hepatocyte-proliferation
#9
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
https://www.readbyqxmd.com/read/27938510/bile-duct-ligation-induces-atz-globule-clearance-in-a-mouse-model-of-%C3%AE-1-antitrypsin-deficiency
#10
Zahida Khan, Shinichiro Yokota, Yoshihiro Ono, Aaron W Bell, Michael Oertel, Donna B Stolz, George K Michalopoulos
α-1 Antitrypsin deficiency (A1ATD) can progress to cirrhosis and hepatocellular carcinoma; however, not all patients are susceptible to severe liver disease. In A1ATD, a toxic gain-of-function mutation generates insoluble ATZ "globules" in hepatocytes, overwhelming protein clearance mechanisms. The relationship between bile acids and hepatocytic autophagy is less clear but may involve altered gene expression pathways. Based on previous findings that bile duct ligation (BDL) induces autophagy, we hypothesized that retained bile acids may have hepatoprotective effects in PiZZ transgenic mice, which model A1ATD...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27938509/sorafenib-and-2-deoxyglucose-synergistically-inhibit-proliferation-of-both-sorafenib-sensitive-and-resistant-hcc-cells-by-inhibiting-atp-production
#11
Ryan Reyes, Nissar A Wani, Kalpana Ghoshal, Samson T Jacob, Tasneem Motiwala
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Sorafenib is the only first-line systemic drug for advanced HCC, but it has very limited survival benefits because patients treated with sorafenib either suffer from side effects or show disease progression after initial response. Thus, there is an urgent need to develop novel strategies for first-line and second-line therapies. The association between sorafenib resistance and glycolysis prompted us to screen several drugs with known antiglycolytic activity to identify those that will sensitize cells to sorafenib...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27938504/knockdown-of-mir-23-mir-27-and-mir-24-alters-fetal-liver-development-and-blocks-fibrosis-in-mice
#12
Charles E Rogler, Joe S Matarlo, Brian Kosmyna, Daniel Fulop, Leslie E Rogler
MicroRNAs (miRNAs) regulate cell fate selection and cellular differentiation. miRNAs of the miR23b polycistron (miR-23b, miR-27b, and miR-24) target components of the TGF-β signaling pathway and affect murine bile ductular and hepatocyte cell fate selection in vitro. Here we show that miR-23b polycistron miRNAs directly target murine Smad4, which is required for TGF-β signaling. Injection of antagomirs against these miRNAs directly into E16.5 murine fetuses caused increased cytokeratin expression in sinusoids and primitive ductular elements throughout the parenchyma of newborn mice...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27938502/novel-advances-in-understanding-of-molecular-pathogenesis-of-hepatoblastoma-a-wnt-%C3%AE-catenin-perspective
#13
Danielle Bell, Sarangarajan Ranganathan, Junyan Tao, Satdarshan P Monga
Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27765085/differential-expression-of-micrornas-in-hepatitis-c-virus-mediated-liver-disease-between-african-americans-and-caucasians-implications-for-racial-health-disparities
#14
Pradip B Devhare, Robert Steele, Adrian M Di Bisceglie, David E Kaplan, Ratna B Ray
African Americans (AAs) have higher hepatocellular carcinoma (HCC) mortality rates than Caucasian Americans (CAs). Chronic hepatitis C virus (HCV) infection leads to cirrhosis and HCC. HCV infection is highly prevalent in the AA population compared to other racial groups. AAs are also less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV. However, the explanation for this disparity is currently unknown. Circulating microRNAs (miRNAs) in the blood are emerging as biomarkers for pathological conditions...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27412505/regulators-of-cholangiocyte-proliferation
#15
Chad Hall, Keisaku Sato, Nan Wu, Tianhao Zhou, Konstantina Kyritsi, Fanyin Meng, Shannon Glaser, Gianfranco Alpini
Cholangiocytes, a small population of cells within the normal liver, have been the focus of a significant amount of research over the past two decades because of their involvement in cholangiopathies such as primary sclerosing cholangitis and primary biliary cholangitis. This article summarizes landmark studies in the field of cholangiocyte physiology and aims to provide an updated review of biliary pathogenesis. The historical approach of rodent extrahepatic bile duct ligation and the relatively recent utilization of transgenic mice have led to significant discoveries in cholangiocyte pathophysiology...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27678082/editorial
#16
Satdarshan Monga, Samson Jacob
No abstract text is available yet for this article.
2016: Gene Expression
https://www.readbyqxmd.com/read/27342733/enhanced-steatosis-and-fibrosis-in-liver-of-adult-offspring-exposed-to-maternal-high-fat-diet
#17
Michael D Thompson, Mary J Cismowski, Aaron J Trask, Scott W Lallier, Amanda E Graf, Lynette K Rogers, Pamela A Lucchesi, David R Brigstock
Early life exposures can increase the risk of developing chronic diseases including nonalcoholic fatty liver disease. Maternal high-fat diet increases susceptibility to development of steatosis in the offspring. We determined the effect of maternal high-fat diet exposure in utero and during lactation on offspring liver histopathology, particularly fibrosis. Female C57Bl/6J mice were fed a control or high-fat diet (HFD) for 8 weeks and bred with lean males. Nursing dams were continued on the same diet with offspring sacrificed during the perinatal period or maintained on either control or high-fat diet for 12 weeks...
2016: Gene Expression
https://www.readbyqxmd.com/read/27302422/myeloid-mixed-lineage-kinase-3-contributes-to-chronic-ethanol-induced-inflammation-and-hepatocyte-injury-in-mice
#18
Rebecca L McCullough, Paramananda Saikia, Katherine A Pollard, Megan R McMullen, Laura E Nagy, Sanjoy Roychowdhury
Proinflammatory activity of hepatic macrophages plays a key role during progression of alcoholic liver disease (ALD). Since mixed lineage kinase 3 (MLK3)-dependent phosphorylation of JNK is involved in the activation of macrophages, we tested the hypothesis that myeloid MLK3 contributes to chronic ethanol-induced inflammatory responses in liver, leading to hepatocyte injury and cell death. Primary cultures of Kupffer cells, as well in vivo chronic ethanol feeding, were used to interrogate the role of MLK3 in the progression of liver injury...
2016: Gene Expression
https://www.readbyqxmd.com/read/27226410/thyroid-hormone-receptor-%C3%AE-agonist-induces-%C3%AE-catenin-dependent-hepatocyte-proliferation-in-mice-implications-in-hepatic-regeneration
#19
Tamara Feliciano Alvarado, Elisabetta Puliga, Morgan Preziosi, Minakshi Poddar, Sucha Singh, Amedeo Columbano, Kari Nejak-Bowen, Satdarshan P S Monga
Triiodothyronine (T3) induces hepatocyte proliferation in rodents. Recent work has shown molecular mechanism for T3's mitogenic effect to be through activation of β-catenin signaling. Since systemic side effects of T3 may preclude its clinical use, and hepatocytes mostly express T3 hormone receptor β (TRβ), we investigated if selective TRβ agonists like GC-1 may also have β-catenin-dependent hepatocyte mitogenic effects. Here we studied the effect of GC-1 and T3 in conditional knockouts of various Wnt pathway components...
2016: Gene Expression
https://www.readbyqxmd.com/read/27197076/zinc-fingers-and-homeoboxes-2-zhx2-regulates-sexually-dimorphic-cyp-gene-expression-in-the-adult-mouse-liver
#20
Kate T Creasy, Jieyun Jiang, Hui Ren, Martha L Peterson, Brett T Spear
The mammalian cytochrome P450 (Cyp) gene family encodes a large number of structurally related enzymes that catalyze a variety of metabolic and detoxification reactions. The liver is the primary site of Cyp expression in terms of expression levels and number of expressed genes, consistent with this organ's essential role in metabolism of endogenous and xenobiotic compounds. Many Cyp genes exhibit sexually dimorphic expression. For example, Cyp2a4 is expressed significantly higher in the adult liver of female mice compared to male mice...
2016: Gene Expression
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