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https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#1
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#2
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#3
Ananthi Rajamoorthi, Noemi Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis, and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#4
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835697/activation-of-perk-nrf2-oncogenic-signaling-promotes-mdm2-mediated-rb-degradation-in-persistently-infected-hcv-culture
#5
Yucel Aydin, Milad Chedid, Srinivas Chava, Donkita Danielle Williams, Shuanghu Liu, Curt H Hagedorn, Suchitra Sumitran-Holgersson, Krzysztof Reiss, Krzysztof Moroz, Hua Lu, Luis A Balart, Srikanta Dash
The mechanism of how chronic hepatitis C virus (HCV) infection leads to such a high rate of hepatocellular carcinoma (HCC) is unknown. We found that the PERK axis of endoplasmic reticulum (ER) stress elicited prominent nuclear translocation of Nrf2 in 100% of HCV infected hepatocytes. The sustained nuclear translocation of Nrf2 in chronically infected culture induces Mdm2-mediated retinoblastoma protein (Rb) degradation. Silencing PERK and Nrf2 restored Mdm2-mediated Rb degradation, suggesting that sustained activation of PERK/Nrf2 axis creates oncogenic stress in chronically infected HCV culture model...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802237/umbelliferon-%C3%AE-d-glucopyranosyl-2-i-%C3%A2-1-ii-%C3%AE-dglucopyranoside-ameliorates-diethylnitrosamine-induced-precancerous-lesion-development-in-liver-via-regulation-of-inflammation-hyperproliferation-and-antioxidant-at-pre-clinical-stage
#6
Vikas Kumar, Prakash Chandra Bhatt, Mahfoozur Rahman, Fahad A Al-Abbasi, Firoz Anwar, Amita Verma
It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2(I)→1(II))-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28752441/pathophysiology-of-alpha-1-antitrypsin-deficiency-liver-disease
#7
Jeffrey H Teckman, Keith S Blomenkamp
Classical alpha-1 antitrypsin (a1AT) deficiency is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults (Teckman and Jain, Curr Gastroenterol Rep 16(1):367, 2014). The vast majority of the liver disease is associated with homozygosity for the Z mutant allele, the so-called PIZZ. These homozygous individuals synthesize large quantities of a1AT mutant Z protein in the liver, but the mutant protein folds improperly during biogenesis and approximately 85% of the molecules are retained within the hepatocytes rather than appropriately secreted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28720429/stable-isotope-based-flux-studies-in-nonalcoholic-fatty-liver-disease
#8
REVIEW
Arthur McCullough, Stephen Previs, Takhar Kasumov
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28627645/therapeutic-strategies-for-alcoholic-liver-disease-focusing-on-inflammation-and-fibrosis-review
#9
Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Masakazu Uejima, Mitsuteru Kitade, Kousuke Takeda, Yasushi Okura, Kousuke Kaji, Hiroaki Takaya, Norihisa Nishimura, Shinya Sato, Yasuhiko Sawada, Kenichiro Seki, Takuya Kubo, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Excessive alcohol consumption is the most common cause of liver disease in the world. Chronic alcohol abuse leads to liver damage, liver inflammation, fibrosis and hepatocellular carcinoma. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, induce liver injury, which leads to the develo-pment of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as interleukin (IL)-6 and IL-10, are also associated with ALD. IL-6 improves ALD via the activation of STAT3 and the subsequent induction of a variety of hepatoprotective genes in hepatocytes...
June 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28617035/measuring-stress-in-young-children-using-hair-cortisol-the-state-of-the-science
#10
Randi Bates, Pamela Salsberry, Jodi Ford
Extensive literature suggests that adverse experiences in early childhood may deleteriously impact later health. These effects are thought to be related to the impact of persistent or chronic stress on various biological processes, mediated by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and ultimately irregularities in cortisol levels. Ameliorating persistent stress in young children requires accurately measuring the chronicity of physiologic stress, which is difficult in young children because of unreliable self-report and the burden and inaccuracy associated with using invasive acute-stress biomeasures...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28604704/thermoneutral-housing-exacerbates-nonalcoholic-fatty-liver-disease-in-mice-and-allows-for-sex-independent-disease-modeling
#11
Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti, David Wu, Rajib Mukherjee, Calvin C Chan, Matthew J Lawson, Jared Klarquist, Annika Sünderhauf, Samir Softic, C Ronald Kahn, Kerstin Stemmer, Yoichiro Iwakura, Bruce J Aronow, Rebekah Karns, Kris A Steinbrecher, Christopher L Karp, Rachel Sheridan, Shiva K Shanmukhappa, Damien Reynaud, David B Haslam, Christian Sina, Jan Rupp, Simon P Hogan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the disease spectrum in humans, including bridging hepatic fibrosis. Here we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high-fat diet (HFD)-induced NAFLD pathogenesis...
July 2017: Nature Medicine
https://www.readbyqxmd.com/read/28587303/the-role-of-lipid-and-lipoprotein-metabolism-in-non-alcoholic-fatty-liver-disease
#12
REVIEW
Francesco Massimo Perla, Maurizia Prelati, Michela Lavorato, Daniele Visicchio, Caterina Anania
Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a "multiple-hit process" where the first "hit" is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity...
June 6, 2017: Children
https://www.readbyqxmd.com/read/28586498/increased-hair-cortisol-concentrations-in-patients-with-progressive-keratoconus
#13
Janine Lenk, Eberhard Spoerl, Tobias Stalder, Susann Schmiedgen, Robert Herber, Lutz E Pillunat, Frederik Raiskup
PURPOSE: To investigate hair cortisol concentration (HCC), a biochemical correlate of chronic psychological stress, and its relationship to the progression of keratoconus. METHODS: Eighty-six participants were included in this prospective observational study (32 patients with progressive keratoconus, 32 patients with stable keratoconus, and 22 healthy controls). Hair cortisol concentrations were determined from 3-cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion during the 3-month period prior to hair sampling...
June 1, 2017: Journal of Refractive Surgery
https://www.readbyqxmd.com/read/28550272/non-alcoholic-fatty-liver-disease-a-chronic-disease-of-the-21-st-century
#14
Peter Metrakos, Tommy Nilsson
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e., cirrhosis, hepatic decompensation (liver failure) and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic...
May 26, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28527050/interplay-between-sirt-3-metabolism-and-its-tumor-suppressor-role-in-hepatocellular-carcinoma
#15
REVIEW
Serena De Matteis, Anna Maria Granato, Roberta Napolitano, Chiara Molinari, Martina Valgiusti, Daniele Santini, Francesco Giuseppe Foschi, Giorgio Ercolani, Umberto Vespasiani Gentilucci, Luca Faloppi, Mario Scartozzi, Giovanni Luca Frassineti, Andrea Casadei Gardini
Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD(+))-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC)...
August 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28487602/hepatitis-b-virus-infection-and-alcohol-consumption
#16
REVIEW
Ayako Iida-Ueno, Masaru Enomoto, Akihiro Tamori, Norifumi Kawada
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C...
April 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28455951/chronic-viral-hepatitis-and-its-association-with-liver-cancer
#17
REVIEW
Thomas Tu, Sandra Bühler, Ralf Bartenschlager
Chronic infection with hepatitis viruses represents the major causative factor for end-stage liver diseases, including liver cirrhosis and primary liver cancer (hepatocellular carcinoma, HCC). In this review, we highlight the current understanding of the molecular mechanisms that drive the hepatocarcinogenesis associated with chronic hepatitis virus infections. While chronic inflammation (associated with a persistent, but impaired anti-viral immune response) plays a major role in HCC initiation and progression, hepatitis viruses can also directly drive liver cancer...
July 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28447325/interferon-free-therapy-with-sofosbuvir-plus-ribavirin-for-successful-treatment-of-genotype-2-hepatitis-c-virus-with-lichen-planus-a-case-report
#18
Ayumu Yoshikawa, Katsumi Terashita, Kenichi Morikawa, Soichiro Matsuda, Takahiro Yamamura, Koichiro Sarashina, Shintaro Nakano, Yoshimitsu Kobayashi, Susumu Sogabe, Kazuhiro Takahashi, Shin Haba, Hisashi Oda, Tatsuro Takahashi, Takuto Miyagishima, Naoya Sakamoto
Hepatitis C virus (HCV) infection remains the main cause of liver disease and can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous system, and immune system. In fact, several studies reported that up to 70% of HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which is an immune system disorder that is triggered by viral infections, allergens, and stress, can affect the skin, mouth, nails, and scalp...
June 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#19
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28373975/increased-erp57-expression-in-hbv-related-hepatocellular-carcinoma-possible-correlation-and-prognosis
#20
Miao Liu, Lingyao Du, Zhiliang He, Libo Yan, Ying Shi, Jin Shang, Hong Tang
Aim. ERp57 is involved in virus induced endoplasmic reticulum stress (ERS) and plays an important role in tumorigenesis. This study aimed to find whether HBV infection altered ERp57 expression and whether ERp57 regulation was involved in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) genesis. Materials and Methods. HBV-HCC tissues, chronic hepatitis B (CHB) liver tissues, and normal liver tissues were acquired. ERp57 expressions in these tissues were detected through immunohistochemistry (IHC)...
2017: BioMed Research International
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