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https://www.readbyqxmd.com/read/28214689/paeoniflorin-ameliorates-cholestasis-via-regulating-hepatic-transporters-and-suppressing-inflammation-in-anit-fed-rats
#1
Yanling Zhao, Xuan He, Xiao Ma, Jianxia Wen, Pengyan Li, Jiabo Wang, Ruisheng Li, Yun Zhu, Shizhang Wei, Haotian Li, Xuelin Zhou, Kun Li, Honghong Liu, Xiaohe Xiao
Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined...
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28213271/woodchuck-sodium-taurocholate-cotransporting-polypeptide-supports-low-level-hepatitis-b-and-d-virus-entry
#2
Liran Fu, Hongjie Hu, Yang Liu, Zhiyi Jing, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP...
February 14, 2017: Virology
https://www.readbyqxmd.com/read/28196288/clinical-adequacy-assessment-of-auto-contours-for-prostate-imrt-with-meaningful-endpoints
#3
Hamidreza Nourzadeh, William T Watkins, Mahmoud Ahmad, Cheukkai Hui, David Schlesinger, Jeffrey V Siebers
PURPOSE: To determine if radiation treatment plans created based on auto-segmented (AS) regions-of-interest (ROI)s are clinically equivalent to plans created based on manually segmented ROIs, where equivalence is evaluated using probabilistic dosimetric metrics and probabilistic biological endpoints for prostate IMRT. METHOD AND MATERIALS: Manually drawn contours and auto-segmented ROIs were created for 167 CT image sets acquired from 19 prostate patients. Auto-segmentation was performed utilizing Pinnacle's Smart Probabilistic Image Contouring Engine...
February 14, 2017: Medical Physics
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#4
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
: Infections with the human Hepatitis B (HBV) and Hepatitis D Virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hNTCP. Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV indicating the requirement of additional HBV-specific factors. As an essential premise towards the establishment for an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28161596/polygoni-multiflori-radix-derived-anthraquinones-alter-bile-acid-disposition-in-sandwich-cultured-rat-hepatocytes
#5
Li Kang, Luqin Si, Jing Rao, Dan Li, Ya Wu, Sanlan Wu, Minghui Wu, Sijie He, Wenwen Zhu, Yang Wu, Jiaqiang Xu, Gao Li, Jiangeng Huang
Hepatic adverse reaction associated with Polygoni Multiflori Radix (PMR) has been frequently reported in recent years. Highly-enriched anthraquinones (AQs) in PMR, such as emodin, chrysophanol and physcion, have been found to be hepatotoxic. In the present study, sandwich-cultured rat hepatocytes (SCRHs) were employed to investigate the effect of individual and combined AQs on the disposition of endogenous bile acids (BAs) and exogenous probe substrates including deuterium-labeled taurocholate (d5-TCA), glycochenodeoxycholic acid (d4-GCDCA) and 5 (and 6)-carboxy-2',7'-dichlorofluorescein (CDF)...
February 2, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28157113/dosimetric-and-radiobiological-comparison-of-cyberknife-and-tomotherapy-in-stereotactic-body-radiotherapy-for-localized-prostate-cancer
#6
Chun-You Chen, Liang-Ming Lee, Hsiao-Wei Yu, Steve P Lee, Hsin-Lun Lee, Yung-Wei Lin, Yu-Ching Wen, Yi-Ju Chen, Chiu-Ping Chen, Jo-Ting Tsai
BACKGROUND AND PURPOSE: As recent studies have suggested relatively low α/β for prostate cancer, the interest in hypofractionated stereotactic body radiotherapy (SBRT) for prostate cancer is rising. The aim of this study is to compare dosimetric results of Cyberknife (CK) with Tomotherapy (HT) in SBRT for localized prostate cancer. Furthermore, the radiobiologic consequences of heterogeneous dose distribution are also analyzed. MATERIAL AND METHOD: A total of 12 cases of localized prostate cancer previously treated with SBRT were collected...
January 31, 2017: Journal of X-ray Science and Technology
https://www.readbyqxmd.com/read/28154180/berberine-induced-inactivation-of-signal-transducer-and-activator-of-transcription-5-signaling-promotes-male-specific-expression-of-a-bile-acid-uptake-transporter
#7
Pengli Bu, Yuan Le, Yue Zhang, Youcai Zhang, Xingguo Cheng
Sodium-taurocholate co-transporting polypeptide (Ntcp/NTCP) is the major uptake transporter of bile salts in mouse and human livers. In certain diseases, including endotoxemia, cholestasis, diabetes, and hepatocarcinoma, Ntcp/NTCP expression is markedly reduced, which interferes with enterohepatic circulation of bile salts, impairing the absorption of lipophilic compounds. Therefore, normal Ntcp/NTCP expression in the liver is physiologically important. Berberine is an herbal medicine used historically to improve liver function and has recently been shown to repress signal transducer and activator of transcription (Stat) signaling...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28149761/impact-of-dose-calculation-models-on-radiotherapy-outcomes-and-quality-adjusted-life-years-for-lung-cancer-treatment-do-we-need-to-measure-radiotherapy-outcomes-to-tune-the-radiobiological-parameters-of-a-normal-tissue-complication-probability-model
#8
Abdulhamid Chaikh, Nicolas Docquière, Pierre-Yves Bondiau, Jacques Balosso
BACKGROUND: The equivalent uniform dose (EUD) radiobiological model can be applied for lung cancer treatment plans to estimate the tumor control probability (TCP) and the normal tissue complication probability (NTCP) using different dose calculation models. Then, based on the different calculated doses, the quality adjusted life years (QALY) score can be assessed versus the uncomplicated tumor control probability (UTCP) concept in order to predict the overall outcome of the different treatment plans...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28125599/n-glycosylation-of-the-na-taurocholate-cotransporting-polypeptide-ntcp-determines-its-trafficking-and-stability-and-is-required-for-hepatitis-b-virus-infection
#9
Monique D Appelman, Anindita Chakraborty, Ulrike Protzer, Jane A McKeating, Stan F J van de Graaf
The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT...
2017: PloS One
https://www.readbyqxmd.com/read/28122566/intentional-avoidance-of-the-esophagus-using-intensity-modulated-radiation-therapy-to-reduce-dysphagia-after-palliative-thoracic-radiation
#10
Patrick V Granton, David A Palma, Alexander V Louie
BACKGROUND: Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the current standard of care using parallel-opposed pair beams (POP)...
January 26, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28121714/hepatitis-delta-and-hiv-infection
#11
Vincent Soriano, Kenneth E Sherman, Pablo Barreiro
Viral liver diseases are frequent co-morbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Whereas cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union and North America, sexual contact has replaced injection drug use has major transmission route for HDV in HIV-positive persons...
January 24, 2017: AIDS
https://www.readbyqxmd.com/read/28110960/dose-effect-analysis-of-radiation-induced-rib-fractures-after-thoracic-sbrt
#12
Barbara Stam, Erik van der Bijl, Heike Peulen, Maddalena M G Rossi, José S A Belderbos, Jan-Jakob Sonke
BACKGROUND AND PURPOSE: To determine a dose-effect relation for radiation induced rib fractures after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC). Automatic rib delineation has enabled the analysis of a large patient group. MATERIAL AND METHODS: Four-hundred and sixty-six patients with stage I/II NSCLC received SBRT with a median of 54Gy in 3 fractions. The optimal EQD2-corrected dose parameter to predict (a)symptomatic fractures was found using Cox regression...
January 19, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28108665/fasiglifam-tak-875-alters-bile-acid-homeostasis-in-rats-and-dogs-a-potential-cause-of-drug-induced-liver-injury
#13
Francis S Wolenski, Andy Z X Zhu, Mike Johnson, Shaoxia Yu, Yuu Moriya, Takuya Ebihara, Vilmos Csizmadia, Jessica Grieves, Martin Paton, Mingxiang Liao, Christopher Gemski, Liping Pan, Majid Vakilynejad, Yvonne P Dragan, Swapan K Chowdhury, Patrick J Kirby
Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations. Repeat dose studies determined that TAK-875 caused a dose-dependent increase in serum total BA in rats and dogs...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28107554/inclusion-of-a-variable-rbe-into-proton-and-photon-plan-comparison-for-various-fractionation-schedules-in-prostate-radiation-therapy
#14
Jakob Ödén, Kjell Eriksson, Iuliana Toma-Dasu
PURPOSE: A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions...
January 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#15
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28081591/new-perspectives-of-biomarkers-for-the-management-of-chronic-hepatitis-b
#16
REVIEW
Chih-Lin Lin, Jia-Horng Kao
With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC...
December 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28077388/the-na-taurocholate-cotransporting-polypeptide-ntcp-slc10a1-ortholog-in-the-marine-skate-leucoraja-erinacea-is-not-a-physiological-bile-salt-transporter
#17
Dongke Yu, Han Zhang, Daniel A Lionarons, James L Boyer, Shi-Ying Cai
The Na(+)-dependent taurocholate co-transporting polypeptide (NTCP/SLC10A1) is a hepatocyte specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of an hepatic Na(+)-dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea. The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28069053/influence-of-daily-imaging-on-plan-quality-and-normal-tissue-toxicity-for-prostate-cancer-radiotherapy
#18
Katharina Bell, Marina Heitfeld, Norbert Licht, Christian Rübe, Yvonne Dzierma
BACKGROUND: Modern radiotherapy offers various possibilities for image guided verification of patient positioning. Different clinically relevant IGRT (image guided radiotherapy) scenarios were considered with regard to their influence on dosimetric plan quality and normal tissue complication probability (NTCP). METHODS: This study is based on treatment plans of 50 prostate patients. We evaluate the clinically performed IGRT and simulate the influence of different daily IGRT scenarios on plan quality...
January 10, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28057404/normal-tissue-complication-probability-ntcp-modelling-of-severe-acute-mucositis-using-a-novel-oral-mucosal-surface-organ-at-risk
#19
J A Dean, L C Welsh, K H Wong, A Aleksic, E Dunne, M R Islam, A Patel, P Patel, I Petkar, I Phillips, J Sham, U Schick, K L Newbold, S A Bhide, K J Harrington, C M Nutting, S L Gulliford
AIMS: A normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR. MATERIALS AND METHODS: Predictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data...
January 2, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28051334/glutamine-attenuates-obstructive-cholestasis-in-rats-via-farnesoid-x-receptor-mediated-regulation-of-bsep-and-mrp2
#20
Bingli Liu, Yiming Li, Hong Ji, Hongwei Lu, Hua Li, Yakun Shi
To investigate the protective effect of glutamine (Gln) against obstructive cholestasis in association with farnesoid X receptor (FXR) activation, an obstructive cholestasis model was established in male Sprague-Dawley rats by bile duct ligation (BDL). Serum biomarkers and hematoxylin plus eosin staining were used to identify the degree of hepatic injury in the rats with obstructive cholestasis after Gln treatment. Immunohistochemistry, real-time PCR, Western blot, cultured primary rat hepatocytes with FXR knockdown, and dual-luciferase reporter assay were performed to elucidate the mechanisms underlying Gln hepatoprotection...
October 5, 2016: Canadian Journal of Physiology and Pharmacology
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