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https://www.readbyqxmd.com/read/28098217/disrupting-hepatocyte-cyp51-from-cholesterol-synthesis-leads-to-progressive-liver-injury-in-the-developing-mouse-and-decreases-rorc-signalling
#1
Žiga Urlep, Gregor Lorbek, Martina Perše, Jera Jeruc, Peter Juvan, Madlen Matz-Soja, Rolf Gebhardt, Ingemar Björkhem, Jason A Hall, Richard Bonneau, Dan R Littman, Damjana Rozman
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H(Cyp51-/-)) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098112/autosomal-dominant-polycystic-kidney-disease-study-of-clinical-characteristics-in-an-indian-population
#2
Sanjay Vikrant, Anupam Parashar
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary form of kidney disease. Clinical data on this multisystem disorder are scarce from developing countries. We conducted a prospective observational study of the clinical profile of ADPKD patients at a single center over a period of six years. A total of 208 patients were studied. Majority were male (60.6%) and the mean age was 45.8 ± 14.5 years. About 61.5% had early stage (Stages 1-3) of chronic kidney disease (CKD) and 38.5% had advanced CKD (Stages 4 and 5)...
January 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28095641/melatonin-ameliorates-alcohol-induced-bile-acid-synthesis-by-enhancing-mir-497-expression
#3
Yong Deuk Kim, Seung-Lark Hwang, Eun-Joo Lee, Hyeong-Mi Kim, Myung-Jin Chung, Ahmed K Elfadl, Sung-Eun Lee, Balachandar Nedumaran, Robert A Harris, Kyu-Shik Jeong
Alcoholic liver disease is a major cause of chronic liver disease worldwide and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression...
January 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28093505/modelling-the-ferrochelatase-c-315-48c-modifier-mutation-for-erythropoietic-protoporphyria-epp-in-mice
#4
Jasmin Barman-Aksözen, Paulina Ćwiek, Vijay B Bansode, Frank Koentgen, Judith Trüb, Pawel Pelczar, Paolo Cinelli, Xiaoye Schneider-Yin, Daniel Schümperli, Elisabeth I Minder
Erythropoietic Protoporphyria (EPP) is caused by deficiency of ferrochelatase (FECH) which incorporates iron into protoporphyrin IX (PPIX) to form heme. Excitation of accumulated PPIX by light generates oxygen radicals which evoke excessive pain and, after longer light exposure, ulcerations in exposed skin areas of EPP patients. Moreover, ∼5% of the patients develop a liver dysfunction due to PPIX accumulation. Most patients (∼97%) have a severe FECH mutation (Mut) in trans to an intronic polymorphism (c...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28090564/hepatocyte-toll-like-receptor-5-promotes-bacterial-clearance-and-protects-mice-against-high-fat-diet-induced-liver-disease
#5
Lucie Etienne-Mesmin, Matam Vijay-Kumar, Andrew T Gewirtz, Benoit Chassaing
BACKGROUND & AIMS: Innate immune dysfunction can promote chronic inflammatory diseases of the liver. For example, mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) show microbial dysbiosis and predisposition to high-fat diet (HFD)-induced hepatic steatosis. The extent to which hepatocytes play a direct role in detecting bacterial products in general, or flagellin in particular, is poorly understood. In the present study, we investigated the role of hepatocyte TLR5 in recognizing flagellin, policing bacteria, and protecting against liver disease...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28088642/anti-rage-antibody-selectively-blocks-acute-systemic-inflammatory-responses-to-lps-in-serum-liver-csf-and-striatum
#6
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Henrique Schaan Fernandes, Alexsander Alves Teixeira, Marcelo Otavio Rodrigues Guasselli, Crepin Aziz Jose O Agani, Natália Cabral Souza, Mateus Grings, Guilhian Leipnitz, Henrique Mautone Gomes, Matheus Augusto de Bittencourt Pasquali, Peter R Dunkley, Phillip W Dickson, José Claudio Fonseca Moreira, Daniel Pens Gelain
Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50 μg/kg) was followed after 1h by a single LPS (5 mg/kg) intraperitoneal injection...
January 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28087365/parasite-induced-increases-in-the-energy-costs-of-movement-of-host-freshwater-fish
#7
Ondřej Slavík, Pavel Horký, Karel Douda, Josef Velíšek, Jitka Kolářová, Pavel Lepič
Parasitization by the larvae (glochidia) of freshwater mussels can cause harm to a fish's gills, resulting in less effective respiration and/or reduced activity by the host fish. The impact of glochidia infections on the host's physiology remains poorly understood, and no information is available concerning energy consumption in parasitized fish. Hence, we obtained glochidia of the invasive unionid mussel Sinanodonta (Anodonta) woodiana and experimentally infected common carp, Cyprinus carpio, tagged with physiological sensors to measure energy consumption...
January 10, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28078997/lipoprotein-a-and-cardiovascular-risk-the-show-must-go-on
#8
Niki Katsiki, Khalid Al-Rasadi, Dimitri P Mikhailidis
Lipoprotein (a) [Lp(a)] is an independent but moderate, predictor for coronary heart disease (CHD) prevalence and severity. Several established and emerging cardiovascular (CV) risk factors including age, gender, ethnicity, smoking, dyslipidemia, hypertension, obesity, type 2 diabetes mellitus, alcohol consumption, arterial stiffness and hyperuricemia have been linked to Lp(a) metabolism. Apart from CHD, Lp(a) has been also associated with non-cardiac vascular diseases and diseases associated with increased CV risk such as chronic kidney disease, metabolic syndrome, non-alcoholic fatty liver disease, erectile dysfunction, obstructive sleep apnea syndrome, inflammatory bowel diseases and human immunodeficiency virus infection...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28077381/metabolic-syndrome-increases-dietary-%C3%AE-tocopherol-requirements-as-assessed-using-urinary-and-plasma-vitamin-e-catabolites-a-double-blind-crossover-clinical-trial
#9
Maret G Traber, Eunice Mah, Scott W Leonard, Gerd Bobe, Richard S Bruno
BACKGROUND: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. OBJECTIVE: We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status...
January 11, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28074870/microrna-155-is-upregulated-in-ascites-in-patients-with-spontaneous-bacterial-peritonitis
#10
Philipp Lutz, Mohamed M Haimid, Alessandra Pohlmann, Jennifer Lehmann, Christian Jansen, Robert Schierwagen, Sabine Klein, Christian P Strassburg, Ulrich Spengler, Jonel Trebicka
MircoRNA's (miR) have been recognised as important modulators of gene expression and potential biomarkers. However, they have been rarely investigated in bio fluids apart from blood. We investigated the association of miR-125b and miR-155 with complications of cirrhosis. Ascites was prospectively collected from patients with cirrhosis undergoing paracentesis at our department. miR's were determined in the supernatant using qPCR and normalized by SV-40. Clinical parameters were assessed at paracentesis and during follow-up...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074668/in-vivo-evidence-of-nephrotoxicity-and-altered-hepatic-function-in-rats-following-administration-of-diglycolic-acid-a-metabolite-of-diethylene-glycol
#11
Corie N Robinson, Brian Latimer, Fleurette Abreo, Kiera Broussard, Kenneth E McMartin
CONTEXT: Diglycolic acid (DGA) is one of the two primary metabolites of diethylene glycol (DEG). DEG is an industrial solvent that has been implicated in mass poisonings resulting from product misuse in the United States and worldwide, with the hallmark toxicity being acute kidney injury, hepatotoxicity, encephalopathy and peripheral neuropathy. Our laboratory has generated in-vitro evidence suggesting that DGA is the metabolite responsible for the proximal tubule necrosis and decreased kidney function observed following DEG ingestion...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#12
Kyunghee Yang, Christina Battista, Jeffrey L Woodhead, Simone H Stahl, Jerome T Mettetal, Paul B Watkins, Scott Q Siler, Brett A Howell
Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Using physiologically-based pharmacokinetic model-predicted drug exposure and enzyme/transporter inhibition constants determined in vitro, our model correctly predicted indinavir-mediated hyperbilirubinemia in humans and rats...
January 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28073931/histones-and-neutrophil-extracellular-traps-enhance-tubular-necrosis-and-remote-organ-injury-in-ischemic-aki
#13
Daigo Nakazawa, Santhosh V Kumar, Julian Marschner, Jyaysi Desai, Alexander Holderied, Lukas Rath, Franziska Kraft, Yutian Lei, Yuichiro Fukasawa, Gilbert W Moeckel, Maria Lucia Angelotti, Helen Liapis, Hans-Joachim Anders
Severe AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organ damage. In hypoxia-induced tubular epithelial cell necrosis in vitro, histone secretion from ischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils...
January 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28073848/cardiac-and-noncardiac-causes-of-long-term-mortality-in-st-segment-elevation-acute-myocardial-infarction-patients-who-underwent-primary-percutaneous-coronary-intervention
#14
Yugo Yamashita, Hiroki Shiomi, Takeshi Morimoto, Hidenori Yaku, Yutaka Furukawa, Yoshihisa Nakagawa, Kenji Ando, Kazushige Kadota, Mitsuru Abe, Kazuya Nagao, Satoshi Shizuta, Koh Ono, Takeshi Kimura
BACKGROUND: In patients with ST-segment-elevation acute myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention, long-term risks for cardiac and noncardiac death beyond acute phase of STEMI have not been thoroughly evaluated yet. METHODS AND RESULTS: We identified 3942 STEMI patients who had primary percutaneous coronary intervention within 24 hours after onset between January 2005 and December 2007 in the CREDO-Kyoto AMI registry (Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction) and evaluated their short-term (within 6-month) and long-term (beyond 6-month) incidences and causes of deaths...
January 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28073175/post-reperfusion-microcirculatory-derangements-after-liver-transplantation-relationship-to-hemodynamics-serum-mediators-and-outcome
#15
Carlo Pulitano, David Joseph, Charbel Sandroussi, Deborah Verran, Phong Ho, Ashe Debiasio, Adriano Luongo, Geoffrey W McCaughan, Nicholas Shackel, Michael Crawford
INTRODUCTION: Despite the growing data supporting the role of microcirculation in regulating liver function, little of this knowledge has been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in-vivo using sidestream dark-field (SDF) imaging and correlate these finding with hepatic blood flow, hemodynamic parameters, and soluble mediators. METHODS: Post-reperfusion hepatic microcirculation was assessed using SDF imaging...
January 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28070495/an-atypical-presentation-of-acad9-deficiency-diagnosis-by-whole-exome-sequencing-broadens-the-phenotypic-spectrum-and-alters-treatment-approach
#16
H K Aintablian, V Narayanan, N Belnap, K Ramsey, T A Grebe
Acyl-CoA dehydrogenase 9 (ACAD9), linked to chromosome 3q21.3, is one of a family of multimeric mitochondrial flavoenzymes that catalyze the degradation of fatty acyl-CoA from the carnitine shuttle via β-oxidation (He et al. 2007). ACAD9, specifically, is implicated in the processing of palmitoyl-CoA and long-chain unsaturated substrates, but unlike other acyl-CoA dehydrogenases (ACADs), it has a significant role in mitochondrial complex I assembly (Nouws et al. 2010 & 2014). Mutations in this enzyme typically cause mitochondrial complex I deficiency, as well as a mild defect in long chain fatty acid metabolism (Haack et al...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28070463/impact-of-birth-weight-and-postnatal-diet-on-the-gut-microbiota-of-young-adult-guinea-pigs
#17
Kait Al, Ousseynou Sarr, Kristyn Dunlop, Gregory B Gloor, Gregor Reid, Jeremy Burton, Timothy R H Regnault
BACKGROUND: The gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse in utero environment such as placental insufficiency resulting in low birth weight (LBW) offspring, contributes to an increased risk of metabolic diseases such as fatty liver infiltration and liver dysfunction in later life...
2017: PeerJ
https://www.readbyqxmd.com/read/28070199/performance-and-utility-of-transient-elastography-and-non-invasive-markers-of-liver-fiibrosis-in-patients-with-autoimmune-hepatitis-a-single-centre-experience
#18
Olympia E Anastasiou, Matthias Büchter, Hideo A Baba, Johannes Korth, Ali Canbay, Guido Gerken, Alisan Kahraman
OBJECTIVES: Autoimmune hepatitis (AIH) is a relatively rare cause of hepatic dysfunction, which can lead to acute liver failure (ALV) and cirrhosis if not treated. The performance of transient elastography (TE) compared to liver biopsy has been evaluated in many liver diseases. The aim of the present study was to evaluate the performance of TE and other non-invasive markers for liver fiibrosis in patients with biopsy-proven AIH. METHODS: Fifty-three patients who were treated at the department of gastroenterology and hepatology of the University Clinic Essen from 2008 to 2013 included in this retrospective study...
November 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/28069746/non-alcoholic-fatty-pancreas-disease
#19
REVIEW
Tamara Alempijevic, Sanja Dragasevic, Simon Zec, Dragan Popovic, Tomica Milosavljevic
Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity...
January 9, 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28069546/g004-a-synthetic-sulfonylurea-compound-exerts-anti-atherosclerosis-effects-by-targeting-sirt1-in-apoe-mice
#20
Lifen Qian, Lingman Ma, Guanzhong Wu, Qian Yu, Huisheng Lin, Qidi Ying, Dan Wen, Cong Gao
Atherosclerosis attracts increasing global attention because of its morbidity and mortality. G004, as a synthetic sulfonylurea compound, has been confirmed to have anti-hyperglycaemia, anti-platelet and anti-thrombus effects. The aim of the present study was to investigate whether G004 suppress the onset and development of atherosclerosis and illuminate its probable mechanism of action. ApoE(-/-) mice that were fed a high-fat diet were randomly divided into five groups by weight; subsequently, they were treated with vehicle, G004, at different doses or atorvastatin once daily for 12weeks...
January 6, 2017: Vascular Pharmacology
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