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Yadira Ansoar-Rodríguez, Cintya A Christofoletti, Jorge E Correia, Raphael B de Souza, Cristina Moreira-de-Sousa, Ana Claudia de Castro Marcato, Odair C Bueno, Osmar Malaspina, Elaine C M Silva-Zacarin, Carmem S Fontanetti
Liver is very sensitive to environmental contaminants such as pesticides, it being the first target of toxicity of a substance. The objective of this study was to investigate the possible effects of the insecticide imidacloprid (IMI) on the liver of Oreochromis niloticus according concentrations used for growing sugarcane. A semi-quantitative analysis of histopathological alterations of IMI on liver was performed by light microscopy and cellular labeling of heat shock proteins (HSP70) by immunohistochemistry...
October 20, 2016: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Adil El Taghdouini, Leo A van Grunsven
Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i...
October 20, 2016: Expert Review of Gastroenterology & Hepatology
Katharina Wolf, Susanne Strand
Generation of primary cell culture of hepatocytes by mouse liver perfusion (MLP) combines the advantages of in vivo and in vitro models. It provides hepatocytes that grow under physiological conditions in mice, with the genotype of the whole organism or a specific gene knockout. In contrast to immortalized cell cultures, primary murine hepatocytes (pmHep) are non-cancerous cells with a limited lifespan but still amenable to classical in vitro methods such as treatment with drugs, small molecule inhibitors, and agonistic/antagonistic antibodies of surface receptors as well as transfection...
2017: Methods in Molecular Biology
Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus...
September 2016: Annals of Translational Medicine
Laurel L Ballantyne, Yuan Yan Sin, Osama Y Al-Dirbashi, Xinzhi Li, David J Hurlbut, Colin D Funk
Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype...
December 2016: Molecular Genetics and Metabolism Reports
Sibghatullah Muhammad Ali Sangi
BACKGROUND: Since long high fat diet (HFD) is being blamed for causing fatty degeneration of liver and formation of atheromatous plaques. At present, no proper pharmacotherapy is available for both the conditions. In this study, different substances containing monounsaturated fatty acids were used to observe their protective effects in the HFD induced damage to liver and coronary vessels. OBJECTIVES: To discover effective therapeutic agents for HFD induced fatty degeneration of liver and atheromatous plaques...
July 2016: Pharmacognosy Magazine
Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
<p>Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
Nikolaos Tsamandouras, Tomasz Kostrzewski, Cynthia L Stokes, Linda G Griffith, David J Hughes, Murat Cirit
In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from 5 different donors cultured in a perfused 3D human liver microphysiological system and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro-in vivo translation. For each donor, metabolic depletion profiles of 6 compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability (LDH release, albumin and urea production)...
October 19, 2016: Journal of Pharmacology and Experimental Therapeutics
Da Zhou, Bing-Hang Li, Jing Wang, Yong-Nian Ding, Yan Dong, Yuan-Wen Chen, Jian-Gao Fan
BACKGROUND: Prolyl oligopeptidase (POP) is a serine endopeptidase that is widely distributed in vivo, particularly in the liver. Significant changes in functional mitochondrial proteins involved with mitochondrial oxidoreductases/transporters and nucleic acid binding proteins were observed after POP inhibition in the liver, which suggested a role of POP in regulating liver energy metabolism. Steatosis in nonalcoholic fatty liver disease (NAFLD) is associated with disturbances in lipid and energy metabolism in hepatocytes...
2016: PloS One
Lily Dara, Zhang-Xu Liu, Neil Kaplowitz
Hepatocyte death, which can be apoptosis or necrosis depending on the context, is a prominent feature of liver disease. The lectin concanavalin A (ConA) activates immune cells, resulting in inflammatory liver injury and hepatocyte necrosis. In this issue of the JCI, Günther et al. demonstrate that the pseudokinase mixed lineage kinase domain-like protein (MLKL) participates in hepatocyte death in ConA injury and that MLKL-mediated death is independent of the receptor-interacting protein kinase RIPK3. RIPK3 was absent in hepatocytes, and MLKL-deficient mice, but not RIPK3-deficient mice, were protected from ConA-induced liver injury...
October 17, 2016: Journal of Clinical Investigation
Nese Karadag, Kerem Tolan, Emine Samdanci, Ayse Selimoglu, Nusret Akpolat, Sezai Yilmaz
OBJECTIVES: Wilson disease is a rare genetic disease with clinical and histopathologic differential diagnostic challenges. In this study, we evaluated the histopathologic findings of explanted livers in Wilson disease, with special emphasis on copper histochemistry. MATERIALS AND METHODS: Our study group was recruited by reviewing archived histopathology reports and the liver transplant clinic patient records retrospectively for patients who had liver transplant for Wilson disease between January 2010 and June 2015, at Turgut Ozal Medical Center...
October 14, 2016: Experimental and Clinical Transplantation
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Delilah F G Hendriks, Lisa Fredriksson Puigvert, Simon Messner, Wolfgang Mortiz, Magnus Ingelman-Sundberg
Drug-induced cholestasis (DIC) is poorly understood and its preclinical prediction is mainly limited to assessing the compound's potential to inhibit the bile salt export pump (BSEP). Here, we evaluated two 3D spheroid models, one from primary human hepatocytes (PHH) and one from HepaRG cells, for the detection of compounds with cholestatic liability. By repeatedly co-exposing both models to a set of compounds with different mechanisms of hepatotoxicity and a non-toxic concentrated bile acid (BA) mixture for 8 days we observed a selective synergistic toxicity of compounds known to cause cholestatic or mixed cholestatic/hepatocellular toxicity and the BA mixture compared to exposure to the compounds alone, a phenomenon that was more pronounced after extending the exposure time to 14 days...
October 19, 2016: Scientific Reports
Gang Chen, Dongsheng Yu, Xue Nian, Junyi Liu, Ronald J Koenig, Bin Xu, Liang Sheng
Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding...
October 19, 2016: Scientific Reports
Yoko Kojima, Koji Okudela, Mai Matsumura, Takahiro Omori, Tomohisa Baba, Akimasa Sekine, Tetsukan Woo, Shigeaki Umeda, Tamiko Takemura, Hideaki Mitsui, Takehisa Suzuki, Yoko Tateishi, Tae Iwasawa, Hiromasa Arai, Michihiko Tajiri, Takashi Ogura, Yoichi Kameda, Munetaka Masuda, Kenich Ohashi
AIMS: To investigate the pathological features of idiopathic interstitial pneumonia (IIP) - associated pulmonary adenocarcinoma. METHODS: Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected. We here further focused on adenocarcinomas that developed in the honeycomb lesions. Adenocarcinomas in the IIP group were subdivided into two groups, one group included tumors connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group) and the other included tumors unrelated to honeycomb lesions (the NH-IIP group)...
October 19, 2016: Histopathology
Jennie Ka Ching Lau, Xiang Zhang, Jun Yu
Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis (NASH) and in more severe cases to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Due to its growing worldwide prevalence, various animal models that mirror both the histopathology and pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field...
October 18, 2016: Journal of Pathology
Zenei Taira, Yukari Ueda, Hiroshi Monmasu, Daisuke Yamase, Sayaka Miyake, Maya Shiraishi
Two specific signals for regulating liver regeneration were found after 70% partial hepatectomy (PH) in rats. The first finding was a sustained increasing signal of intracellular Ca(2+) ([Ca(2+)]i) in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. The second finding was an abnormal peak in the restoring ratio (Rr) curve of liver regeneration after 70% PH at day 4, where the Rr exceeded 100% temporarily, returned to a lower level, and then proceeded to a termination phase of liver regeneration...
2016: Journal of Experimental Pharmacology
Yanning Li, Zhigang Xiao, Bin Li, Kun Liu, Hui Wang, Jinsheng Qi, Yu Wang
Although ginsenoside can generally promote cell proliferation, it is reported to have anti-proliferative effects in hepatocellular carcinoma (HCC). Whether ginsenoside has concentration-dependent effects on HCC cell proliferation have not been clarified. Transcription factors c-Myc and hepatocyte nuclear factor (HNF)-4α are the most important opposite controllers of HCC cell proliferation. Whether and how ginsenoside regulates c-Myc and HNF-4α as well as their recruitment of the co-activator p300 to exhibit its effects on HCC cell proliferation are pending...
October 15, 2016: European Journal of Pharmacology
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