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https://www.readbyqxmd.com/read/28338936/establishment-of-a-human-hepatocellular-cell-line-capable-of-maintaining-long-term-replication-of-hepatitis-b-virus
#1
Wan-Ling Yao, Sotaro Ikeda, Yuta Tsukamoto, Keiko Shindo, Yukie Otakaki, Main Qin, Yoshikazu Iwasawa, Fumihiko Takeuchi, Yuki Kaname, Yu-Chi Chou, Chungming Chang, Koichi Watashi, Takaji Wakita, Takeshi Noda, Hiroki Kato, Takashi Fujita
Hepatitis B virus is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells overexpressing HBV entry receptor human NTCP, and defective in RIG-I-like receptor signaling, by knocking down the IPS-1 adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBc expression...
March 11, 2017: International Immunology
https://www.readbyqxmd.com/read/28337145/dioscin-protects-anit-induced-intrahepatic-cholestasis-through-regulating-transporters-apoptosis-and-oxidative-stress
#2
Hong Yao, Youwei Xu, Lianhong Yin, Xufeng Tao, Lina Xu, Yan Qi, Xu Han, Pengyuan Sun, Kexin Liu, Jinyong Peng
Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28302211/-sodium-taurocholate-cotransporting-polypeptide-deficiency-manifesting-as-cholestatic-jaundice-in-early-infancy-a-complicated-case-study
#3
Yuan-Zong Song, Mei Deng
Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is caused by SLC10A1 mutations impairing the NTCP function to uptake plasma bile salts into the hepatocyte. Thus far, patients with NTCP deficiency were rarely reported. The patient in this paper was a 5-month-19-day male infant with the complaint of jaundiced skin and sclera for 5.5 months as well as abnormal liver function revealed over 4 months. His jaundice was noticed on the second day after birth, and remained visible till his age of 1 month and 13 days, when a liver function test unveiled markedly elevated total, direct and indirect bilirubin as well as total bile acids (TBA)...
March 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28293971/a-modeling-study-of-functional-magnetic-resonance-imaging-to-individualize-target-definition-of-seminal-vesicles-for-external-beam-radiotherapy
#4
Sidsel Damkjær, Jakob B Thomsen, Svetlana I Petersen, Jens Peter Bangsgaard, Peter M Petersen, Ivan R Vogelius, Marianne C Aznar
BACKGROUND: Pre-treatment magnetic resonance imaging (MRI) can give patient-specific evaluation of suspected pathologically involved volumes in the seminal vesicles (SV) in prostate cancer patients. By targeting this suspicious volume we hypothesize that radiotherapy is more efficient without introducing more toxicity. In this study we evaluate the concept of using MRI-defined target volumes in terms of tumor control probability (TCP) and rectal normal tissue complication probability (NTCP)...
March 15, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28291917/rectal-dose-to-prostate-cancer-patients-treated-with-proton-therapy-with-or-without-rectal-spacer
#5
Heeteak Chung, Jerimy Polf, Shahed Badiyan, Matthew Biagioli, Daniel Fernandez, Kujtim Latifi, Richard Wilder, Minesh Mehta, Michael Chuong
The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields...
January 2017: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28289714/bile-acids-initiate-cholestatic-liver-injury-by-triggering-a-hepatocyte-specific-inflammatory-response
#6
Shi-Ying Cai, Xinshou Ouyang, Yonglin Chen, Carol J Soroka, Juxian Wang, Albert Mennone, Yucheng Wang, Wajahat Z Mehal, Dhanpat Jain, James L Boyer
Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2(-/-) mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28281862/model-based-approach-for-quantitative-estimates-of-skin-heart-and-lung-toxicity-risk-for-left-side-photon-and-proton-irradiation-after-breast-conserving-surgery
#7
Francesco Tommasino, Marco Durante, Vittoria D'Avino, Raffaele Liuzzi, Manuel Conson, Paolo Farace, Giuseppe Palma, Marco Schwarz, Laura Cella, Roberto Pacelli
BACKGROUND: Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. MATERIAL AND METHODS: Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database...
March 10, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28273180/synthesis-in-vitro-and-in-vivo-evaluation-of-3%C3%AE-18f-fluorocholic-acid-for-the-detection-of-drug-induced-cholestasis-in-mice
#8
Stef De Lombaerde, Sara Neyt, Ken Kersemans, Jeroen Verhoeven, Lindsey Devisscher, Hans Van Vlierberghe, Christian Vanhove, Filip De Vos
INTRODUCTION: Drug-induced cholestasis is a liver disorder that might be caused by interference of drugs with the hepatobiliary bile acid transporters. It is important to identify this interference early on in drug development. In this work, Positron Emission Tomography (PET)-imaging with a 18F labeled bile acid analogue was introduced to detect disturbed hepatobiliary transport of bile acids. METHODS: 3β-[18F]fluorocholic acid ([18F]FCA) was prepared by nucleophilic substitution of a mesylated precursor with [18F]fluoride, followed by deprotection with sodium hydroxide...
2017: PloS One
https://www.readbyqxmd.com/read/28262508/the-role-of-ntcp-oatp2-bsep-and-mrp2-in-liver-injury-induced-by-dioscorea-bulbifera-l-and-diosbulbin-b-in-mice
#9
Xiao-Yu Qu, Li-Na Tao, Si-Xi Zhang, Jing-Meng Sun, Jun-Qi Niu, Yan-Hua Ding, Yan-Qing Song
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels...
February 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28249806/application-of-quantitative-targeted-absolute-proteomics-to-profile-protein-expression-changes-of-hepatic-transporters-and-metabolizing-enzymes-during-cholic-acid-promoted-liver-regeneration
#10
Takayuki Miura, Masanori Tachikawa, Hideo Ohtsuka, Koji Fukase, Shun Nakayama, Naoaki Sakata, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, Yasuo Uchida, Sumio Ohtsuki, Tetsuya Terasaki, Michiaki Unno
Preoperative administration of cholic acid (CA) may be an option to increase the liver volume before elective liver resection surgery, so it is important to understand its effects on liver functionality for drug transport and metabolism. The purpose of this study was to clarify the absolute protein expression dynamics of transporters and metabolizing enzymes in the liver of mice fed CA-containing diet for 5 days (CA1) and mice fed CA-containing diet for 5 days followed by diet without CA for 7 days (CA2), in comparison with non CA-fed control mice...
February 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28249291/bile-acid-uptake-transporters-as-targets-for-therapy
#11
Davor Slijepcevic, Stan F J van de Graaf
Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249272/extended-abstract-deficiency-of-sodium-taurocholate-cotransporting-polypeptide-slc10a1-a-new-inborn-error-of-metabolism-with-an-attenuated-phenotype
#12
Frédéric M Vaz, Hidde H Huidekoper, Coen C Paulusma
We present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28243318/mixed-methods-for-comparing-tobacco-cessation-interventions
#13
Behnoosh Momin, Antonio Neri, Lei Zhang, Jennifer Kahende, Jennifer Duke, Sonya Goode Green, Ann Malarcher, Sherri L Stewart
INTRODUCTION: The National Comprehensive Cancer Control Program (NCCCP) and National Tobacco Control Program (NTCP) are both well-positioned to promote the use of population-based tobacco cessation interventions, such as state quitlines and Web-based interventions. AIMS: This paper outlines the methodology used to conduct a comparative effectiveness research study of traditional and Web-based tobacco cessation and quitline promotion approaches. METHODS: A mixed-methods study with three components was designed to address the effect of promotional activities on service usage and the comparative effectiveness of population-based smoking cessation activities across multiple states...
March 2017: Journal of Smoking Cessation
https://www.readbyqxmd.com/read/28237774/identification-of-urine-tauro-%C3%AE-muricholic-acid-as-a-promising-biomarker-in-polygoni-multiflori-radix-induced-hepatotoxicity-by-targeted-metabolomics-of-bile-acids
#14
Dong-Sheng Zhao, Li-Long Jiang, Ya-Xi Fan, Lei-Chi Dong, Jiang Ma, Xin Dong, Xiao-Jun Xu, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been widely used as a tonic for centuries. However, hepatotoxicity cases linked to PMR have been frequently reported and appropriate biomarkers for clinical diagnosis are currently lacking. Here, an approach using UPLC-QqQ/MS-based targeted metabolomics of bile acids (BAs) complemented with biochemistry and histopathology was applied to characterize the development and recovery processes of PMR-induced hepatotoxicity in rats and to identify biomarkers. The expression of bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) were evaluated to investigate the underlying mechanism...
February 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28236658/targeted-dose-enhancement-in-radiotherapy-for-breast-cancer-using-gold-nanoparticles-part-2-a-treatment-planning-study
#15
Lidia Strigari, Veronica Ferrero, Giovanni Visonà, Piergiorgio Cerello, Andrea Attili, Sonja Visentin
PURPOSE: In recent years there has been growing interest in the use of gold nanoparticles (GNPs) combined with radiotherapy to improve tumor control. However, the complex interplay between GNP uptake and dose distribution in realistic clinical treatment are still somewhat unknown. METHODS: The effects of different concentrations of 2 nm diameter GNP, ranging from 0 to 5x10(5) nanoparticles per tumoral cell, were theoretically investigated. A parametrization of the GNP distribution outside the target was carried out using a Gaussian standard deviation σ, from a zero value, relative to a selective concentration of GNPs inside the tumor volume alone, to 50 mm, when GNPs are spatially distributed also in the healthy tissues surrounding the tumor...
February 25, 2017: Medical Physics
https://www.readbyqxmd.com/read/28214689/paeoniflorin-ameliorates-cholestasis-via-regulating-hepatic-transporters-and-suppressing-inflammation-in-anit-fed-rats
#16
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
#17
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
#18
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
#19
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
#20
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
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