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alpha-1 liver disease

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https://www.readbyqxmd.com/read/28337300/mutation-of-mir-21-targets-endogenous-lipoprotein-receptor-related-protein-6-and-nonalcoholic-fatty-liver-disease
#1
Chang-Ping Li, Hong-Jue Li, Jiao Nie, Xia Chen, Xian Zhou
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#2
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28328804/liver-function-in-alpha-1-antitrypsin-deficient-individuals-at-37-to-40-years-of-age
#3
Behrouz Mostafavi, Sandra Diaz, Hanan A Tanash, Eeva Piitulainen
Severe alpha-1-antitrypsin (AAT) deficiency (PiZZ) is a risk factor for liver disease, but the prevalence of liver cirrhosis and hepatocellular cancer in PiZZ adults is unknown. The risk of liver disease in adults with moderate AAT deficiency (PiSZ) is also unknown. A cohort of 127 PiZZ, 2 PiZnull, 54 PiSZ, and 1 PiSnull individuals were identified by the Swedish national neonatal AAT screening program between 1972 and 1974, when all 200,000 newborn infants in Sweden were screened for AAT deficiency. The cohort has been followed up since birth...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28326955/a-challenging-case-of-severe-infantile-cholestasis-in-alpha-1-antitrypsin-deficiency
#4
Zahida Khan, Veena L Venkat, Kyle A Soltys, Donna B Stolz, Sarangarajan Ranganathan
Jaundice in the newborn period can be physiologic and is often due to benign causes. Jaundice due to conjugated hyperbilirubinemia extending beyond the second week of life may be an early sign of several cholestatic or metabolic liver diseases, and it requires logical and timely analysis so that specific treatments can be initiated. Alpha-1 antitrypsin deficiency is the most common genetic cause of pediatric liver disease and transplantation, and it must be considered when evaluating cholestatic infants. Here, we present an unusual case of alpha-1 antitrypsin deficiency with severe infantile cholestasis and rapid decompensation in the first 4 months of life, where in-depth but timely diagnosis was crucial for the appropriate intervention to take place...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28306355/alpha-1-antitrypsin-deficiency-disease-management-and-learning-from-studies
#5
Timm Greulich
Alpha-1-antitrypsin deficiency (AATD) is one of the most frequent genetic causes of liver and lung diseases. Despite its known association with chronic obstructive pulmonary disease (COPD), AATD is largely unrecognised and underdiagnosed. Cases of AATD exist within every COPD or spirometry population but must be actively investigated. AATD is a laboratory diagnosis that must be confirmed by a blood test. A number of clinical 'clues' can raise suspicion of AATD, potentially facilitating earlier diagnosis and initiation of appropriate treatment...
March 15, 2017: COPD
https://www.readbyqxmd.com/read/28301738/active-immunization-against-transforming-growth-factor-beta1-prevents-hepatic-fibrosis-in-a-rat-model-of-liver-disease
#6
Hong Ji, Gerald Y Minuk, Zhikang Peng, Yongping Chen, Chenwei Pan, Yuewen Gong
Transforming growth factor-beta1 (TGF-β1) plays an important role in hepatic fibrogenesis. To document the effects of active immunization against TGF-β1 on hepatic fibrosis in an animal model of chronic liver disease. BALB/c mice were immunized against three different peptides of TGF-β1 ligated into hepatitis B virus core protein (HBVc). Titers of TGF-β1 antibodies were documented by enzyme linked immunoassays and antibody activity by cell membrane receptor binding and proliferation assays. The most immunogenic recombinant HBVc+TGF-β1 peptide (HBVc+C) then served as a vaccine in Sprague-Dawley rats with dimethylnitrosamine-induced chronic liver disease...
March 16, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28301499/svip-regulates-z-variant-alpha-1-antitrypsin-retro-translocation-by-inhibiting-ubiquitin-ligase-gp78
#7
Nazli Khodayari, Rejean Liqun Wang, George Marek, Karina Krotova, Mariana Kirst, Chen Liu, Farshid Rouhani, Mark Brantly
Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by early-onset emphysema and liver disease. The most common disease-causing mutation is a single amino acid substitution (Glu/Lys) at amino acid 342 of the mature protein, resulting in disruption of the 290-342 salt bridge (an electrophoretic abnormality defining the mutation [Z allele, or ZAAT]), protein misfolding, polymerization, and accumulation in the endoplasmic reticulum of hepatocytes and monocytes. The Z allele causes a toxic gain of function, and the E3 ubiquitin ligase gp78 promotes degradation and increased solubility of endogenous ZAAT...
2017: PloS One
https://www.readbyqxmd.com/read/28295152/causally-treatable-hereditary-neuropathies-in-fabry-s-disease-transthyretin-related-familial-amyloidosis-and-pompe-s-disease
#8
REVIEW
J Finsterer, J Wanschitz, S Quasthoff, S Iglseder, W Löscher, W Grisold
OBJECTIVES: Most acquired neuropathies are treatable, whereas genetic neuropathies respond to treatment in Fabry's disease (FD), transthyretin-related familial amyloidosis (TTR-FA), and Pompe's disease (PD). This review summarizes and discusses recent findings and future perspectives concerning etiology, pathophysiology, clinical presentation, diagnosis, treatment, and outcome of neuropathy in FD, TTR-FA, and PD. METHODS: Literature review. RESULTS: Neuropathy in FD concerns particularly small, unmyelinated, or myelinated sensory fibers (small fiber neuropathy [SFN]) and autonomic fibers, manifesting as acroparesthesias, Fabry's crises, or autonomous disturbances...
March 12, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28285495/pharmacological-interventions-for-acute-hepatitis-c-infection-an-attempted-network-meta-analysis
#9
REVIEW
Maria Kalafateli, Elena Buzzetti, Douglas Thorburn, Brian R Davidson, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood...
March 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28278289/toyocamycin-attenuates-free-fatty-acid-induced-hepatic-steatosis-and-apoptosis-in-cultured-hepatocytes-and-ameliorates-nonalcoholic-fatty-liver-disease-in-mice
#10
Ikuko Takahara, Yuko Akazawa, Maiko Tabuchi, Katsuya Matsuda, Hisamitsu Miyaaki, Youko Kido, Yasuko Kanda, Naota Taura, Ken Ohnita, Fuminao Takeshima, Yusuke Sakai, Susumu Eguchi, Masahiro Nakashima, Kazuhiko Nakao
BACKGROUND AND AIMS: A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α...
2017: PloS One
https://www.readbyqxmd.com/read/28273032/the-efficacy-of-modified-docetaxel-cisplatin-5-fluorouracil-regimen-as-first-line-treatment-in-patients-with-alpha-fetoprotein-producing-gastric-carcinoma
#11
Yakup Bozkaya, Mutlu Doğan, Ozan Yazıcı, Gökmen Umut Erdem, Nebi Serkan Demirci, Nurullah Zengin
Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients...
February 25, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28264879/abcg1-regulates-pulmonary-surfactant-metabolism-in-mice-and-men
#12
Thomas Q de Aguiar Vallim, Elinor Lee, David J Merriott, Christopher N Goulbourne, Joan Cheng, Angela Cheng, Ayelet Gonen, Ryan M Allen, Elisa N D Palladino, David A Ford, Tisha Wang, Ángel Baldán, Elizabeth J Tarling
Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 pneumocytes (T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ATP Binding Cassette Transporter G1 (ABCG1) is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes and immunoglobulins, clearly demonstrating ABCG1 has a critical role in pulmonary homeostasis...
March 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28260452/unusual-indications-for-a-liver-transplant-a-single-center-experience
#13
Aydincan Akdur, Mahir Kirnap, Ebru H Ayvazoglu Soy, Figen Ozcay, Gokhan Moray, Gulnaz Arslan, Mehmet Haberal
OBJECTIVES: This study sought to evaluate the efficacy of liver transplant for unusual liver diseases. MATERIALS AND METHODS: The results of 476 patients who underwent liver transplant from 1988 to January 2015 were retrospectively analyzed. Two hundred forty-five of them were adult patients and 231 of them were pediatric. Thirty-one patients had unusual liver disease. RESULTS: Of the 31 patients with unusual liver disease, 9 (29%) were adult and 22 (71%) were pediatric patients...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28240761/hepatocellular-carcinoma-and-cxcr3-chemokines-a-narrative-review
#14
E Giusy, F Poupak
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3)...
January 2017: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28225186/randomised-clinical-trial-the-efficacy-and-safety-of-oltipraz-a-liver-x-receptor-alpha-inhibitory-dithiolethione-in-patients-with-non-alcoholic-fatty-liver-disease
#15
W Kim, B G Kim, J S Lee, C K Lee, J E Yeon, M S Chang, J H Kim, H Kim, S Yi, J Lee, J-Y Cho, S G Kim, J-H Lee, Y J Kim
BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study...
February 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28213164/carvedilol-use-is-associated-with-improved-survival-in-patients-with-liver-cirrhosis-and-ascites
#16
Rohit Sinha, Khalida A Lockman, Nethmee Mallawaarachchi, Marcus Robertson, John N Plevris, Peter C Hayes
BACKGROUND & AIMS: Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality. METHODS: A single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012 was carried out...
February 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signaling-and-promotes-lipid-accumulation-in-hepatocytes
#17
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28195199/pemafibrate-a-novel-selective-peroxisome-proliferator-activated-receptor-alpha-modulator-improves-the-pathogenesis-in-a-rodent-model-of-nonalcoholic-steatohepatitis
#18
Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Kento Imajo, Koji Fujita, Masato Yoneda, Toshiaki Takizawa, Satoru Saito, Yoji Nagashima, Atsushi Nakajima
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181486/high-expression-of-akr1b10-predicts-low-risk-of-early-tumor-recurrence-in-patients-with-hepatitis-b-virus-related-hepatocellular-carcinoma
#19
Yan-Yan Wang, Lu-Nan Qi, Jian-Hong Zhong, Hong-Gui Qin, Jia-Zhou Ye, Shi-Dong Lu, Liang Ma, Bang-De Xiang, Le-Qun Li, Xue-Mei You
To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178643/elevated-serum-visfatin-levels-are-associated-with-poor-prognosis-of-hepatocellular-carcinoma
#20
Yifan Sun, Shengbo Zhu, Zhitong Wu, Yiyong Huang, Chunming Liu, Shifu Tang, Lili Wei
Visfatin is considered a pro-inflammatory adipocytokine, and it is commonly increased in obesity-related diseases. This study aimed to evaluate the levels of serum visfatin in patients with hepatocellular carcinoma (HCC) and its diagnostic and predictive value in detecting HCC. Fasting serum levels of visfatin of 135 HCC patients, 115 chronic hepatitis B (CHB) patients, 129 liver cirrhosis (LC) patients, and 149 healthy controls were determined via enzyme-linked immunosorbent assay. Meanwhile, serum alpha fetal protein (AFP) and interleukin-6 (IL-6) were also assayed...
February 4, 2017: Oncotarget
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