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https://www.readbyqxmd.com/read/29786754/regulation-of-interferon-signaling-and-hcv%C3%A2-rna-replication-by-extracellular-matrix
#1
Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki
Although interferon (IFN)‑based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH‑7 human hepatoma cell line and HuH‑7 cells were stably transfected with full‑length HCV‑RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM‑coated dishes or non‑coated plastic dishes (NDs), and treated with human IFN‑α...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#2
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784423/microwave-assisted-solid-phase-synthesis-of-highly-fluorescent-carbon-nanoparticles-and-its-application-in-intracellular-ph-sensing
#3
Shenghong Yang, Xiao Chen, Shuqin Liu, Fuxin Wang, Gangfeng Ouyang
Fluorescent carbon nanoparticles (FCNPs) have been deeply researched and widely applied in recent years due to their good optics performance, chemical stability and biocompatibility. Herein, a green and rapid microwave-assisted solid-phase synthesis (solvent-free) approach was proposed for the fabrication of highly FCNPs in a very short period of time, 4 min. The as-prepared FCNPs can emit a blue emission with quantum yield of up to 63.2% in water solution and show yellow fluorescence in the solid state. The FCNPs also exhibit special solvent effect that the fluorescence emission can be adjusted by controlling the solvent ratio of ethanol and water...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29781585/group-i-paks-support-muscle-regeneration-and-counteract-cancer-associated-muscle-atrophy
#4
Andrea Cerquone Perpetuini, Andrea David Re Cecconi, Michela Chiappa, Giulia Benedetta Martinelli, Claudia Fuoco, Giovanni Desiderio, Luisa Castagnoli, Cesare Gargioli, Rosanna Piccirillo, Gianni Cesareni
BACKGROUND: Skeletal muscle is characterized by an efficient regeneration potential that is often impaired during myopathies. Understanding the molecular players involved in muscle homeostasis and regeneration could help to find new therapies against muscle degenerative disorders. Previous studies revealed that the Ser/Thr kinase p21 protein-activated kinase 1 (Pak1) was specifically down-regulated in the atrophying gastrocnemius of Yoshida hepatoma-bearing rats. In this study, we evaluated the role of group I Paks during cancer-related atrophy and muscle regeneration...
May 21, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29780557/pd-nanosheets-with-their-surface-coordinated-by-radioactive-iodide-as-a-high-performance-theranostic-nanoagent-for-orthotopic-hepatocellular-carcinoma-imaging-and-cancer-therapy
#5
Mei Chen, Zhide Guo, Qinghua Chen, Jingping Wei, Jingchao Li, Changrong Shi, Duo Xu, Dawang Zhou, Xianzhong Zhang, Nanfeng Zheng
Radiolabeled nanoparticles (NPs), taking advantage of nanotechnology and nuclear medicine, have shown attractive potential for cancer diagnosis and therapy. However, the high background signal in the liver and long-term toxic effects of radioisotopes caused by the nonselective accumulation of radiolabeled nanoparticles in organs have become the major challenges. Here, we report a pH-sensitive multifunctional theranostic platform with radiolabeled Pd nanosheets through a simple mixture of ultra-small Pd nanosheets and radioisotopes utilizing the strong adsorption of 131 I and 125 I on their surfaces (denoted as 131 I-Pd-PEG or 125 I-Pd-PEG)...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29778027/influence-of-gastrointestinal-tract-on-metabolism-of-bisphenol-a-as-determined-by-in-vitro-simulated-system
#6
Yonghua Wang, Min Rui, Yang Nie, Guanghua Lu
Oral exposure is a major route of human bisphenol A (BPA) exposure. However, influence of gastrointestinal tract on BPA metabolism is unavailable. In this study, in vitro simulator of the human intestinal microbial ecosystem (SHIME) was applied to investigate the changes in bioaccessibility and metabolism of BPA in different parts of gastrointestinal tract (stomach, small intestine and colon). Then the human hepatoma cell line HepG2 was employed to compare toxic effects of BPA itself and effluents of SHIME system on hepatic gene expression profiles...
May 7, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29774518/huh-7-reference-genome-profile-complex-karyotype-composed-of-massive-loss-of-heterozygosity
#7
Fumio Kasai, Noriko Hirayama, Midori Ozawa, Motonobu Satoh, Arihiro Kohara
Human cell lines represent a valuable resource as in vitro experimental models. A hepatoma cell line, HuH-7 (JCRB0403), has been used extensively in various research fields and a number of studies using this line have been published continuously since it was established in 1982. However, an accurate genome profile, which can be served as a reliable reference, has not been available. In this study, we performed M-FISH, SNP microarray and amplicon sequencing to characterize the cell line. Single cell analysis of metaphases revealed a high level of heterogeneity with a mode of 60 chromosomes...
May 17, 2018: Human Cell
https://www.readbyqxmd.com/read/29772801/ogt-o-glcnac-transferase-selectively-modifies-multiple-residues-unique-to-lamin-a
#8
Dan N Simon, Amanda Wriston, Qiong Fan, Jeffrey Shabanowitz, Alyssa Florwick, Tejas Dharmaraj, Sherket B Peterson, Yosef Gruenbaum, Cathrine R Carlson, Line M Grønning-Wang, Donald F Hunt, Katherine L Wilson
The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails...
May 17, 2018: Cells
https://www.readbyqxmd.com/read/29772274/pharmacodynamic-and-pharmacokinetic-characteristics-of-ymr-65-a-tubulin-inhibitor-in-tumor-bearing-mice
#9
Ali Fan, Jiali Wei, Mengru Yang, Qing Zhang, Yaliang Zhang, Qingwang Liu, Ning Li, Di Zhao, Yang Lu, Junxiu Li, Jie Zhao, Shuhua Deng, Bingjie Zhang, Hailiang Zhu, Xijing Chen
YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a potential tubulin inhibitor exhibiting good anticancer activity. In our study, we illustrated the biological activities in HepG2 cells and the pharmacodynamic and pharmacokinetic profiles were evaluated in murine H22 hepatoma-bearing mice. Molecular docking assay and colchicine competition assay indicated that YMR-65 could bind tightly to the colchicine binding site of tubulin. Further investigation demonstrated that YMR-65 arrested cells in the G2/M phase of cell cycle and induced apoptosis in HepG2 cells...
May 14, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29771984/dna-methylation-of-hepatic-iron-sensing-genes-and-the-regulation-of-hepcidin-expression
#10
Paul A Sharp, Rachel Clarkson, Ahmed Hussain, Robert J Weeks, Ian M Morison
Production of the iron regulatory peptide hepcidin is tightly controlled by a network of proteins in hepatocytes that sense levels of iron in the circulation (as diferric-transferrin) and in tissues (in ferritin). Human studies show high variability in the normal range of serum hepcidin levels. We have postulated that this may, in part, be related to inter-individual variability in the expression of genes in the iron sensing pathway, potentially governed by epigenetic factors. Here, we have investigated whether genes encoding hepatic iron sensing proteins and hepcidin are regulated by DNA methylation...
2018: PloS One
https://www.readbyqxmd.com/read/29771951/antitumor-antioxidant-and-anti-inflammatory-activities-of-kaempferol-and-its-corresponding-glycosides-and-the-enzymatic-preparation-of-kaempferol
#11
Jingqiu Wang, Xianying Fang, Lin Ge, Fuliang Cao, Linguo Zhao, Zhenzhong Wang, Wei Xiao
Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells...
2018: PloS One
https://www.readbyqxmd.com/read/29765517/targeting-the-mevalonate-pathway-is-a-novel-therapeutic-approach-to-inhibit-oncogenic-foxm1-transcription-factor-in-human-hepatocellular-carcinoma
#12
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761789/ph-and-redox-responsive-nanoparticles-composed-of-charge-reversible-pullulan-based-shells-and-disulfide-containing-poly-%C3%AE-amino-ester-cores-for-co-delivery-of-gene-and-chemotherapeutic-agent
#13
Sipei Zhang, Dan Wang, Yating Li, Ling Li, Hongli Chen, Qingqing Xiong, Yuan-Yuan Liu, Yingsong Wang
A novel pH- and redox-responsive nanoparticle system was designed based on charge-reversible pullulan derivative (CAPL) and disulfide-containing poly(β-amino ester) (ssPBAE) for the co-delivery of gene and chemotherapeutic agent targeting hepatoma. The end-alkene groups of ssPBAE were reacted with diethylenetriamine to form amino-modified ssPBAE (NH-ssPBAE). Methotrexate (MTX), a chemotherapy agent, was then conjugated to NH-ssPBAE via amide bond to obtain a polymeric prodrug ssPBAE-MTX. ssPBAE-MTX exhibited a good capability for condensing genes including plasmid DNA (pDNA) and tetramethyl rhodamine-labeled DNA (TAMRA-DNA), and almost completely condensed pDNA at the weight ratio of 5/1 to form spherical nanocomplexes with an uniform size...
May 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#14
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29761175/anti-tumoral-effects-of-exercise-on-hepatocellular-carcinoma-growth
#15
Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V St-Pierre, Jean-François Dufour
Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups...
May 2018: Hepatology communications
https://www.readbyqxmd.com/read/29760415/rbm24-stabilizes-hepatitis-b-virus-pregenomic-rna-but-inhibits-core-protein-translation-by-targeting-the-terminal-redundancy-sequence
#16
Yongxuan Yao, Bo Yang, Huang Cao, Kaitao Zhao, Yifei Yuan, Yingshan Chen, Zhenhua Zhang, Yun Wang, Rongjuan Pei, Jizheng Chen, Xue Hu, Yuan Zhou, Mengji Lu, Chunchen Wu, Xinwen Chen
The terminal redundancy (TR) sequence of the 3.5-kb hepatitis B virus (HBV) RNA contains sites that govern many crucial functions in the viral life cycle, including polyadenylation, translation, RNA packaging, and DNA synthesis. In the present study, RNA-binding motif protein 24 (RBM24) is shown to be involved in the modulation of HBV replication by targeting the TR of HBV RNA. In HBV-transfected hepatoma cell lines, both knockdown and overexpression of RBM24 led to decreased HBV replication and transcription...
May 14, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29753013/transferrin-anchored-poly-lactide-micelles-to-improve-anticancer-activity-of-curcumin-in-hepatic-and-cervical-cancer-cell-monolayers-and-3d-spheroids
#17
Preeti Kumari, Sri Vishnu Kiran Rompicharla, Omkara Swami Muddineti, Balaram Ghosh, Swati Biswas
In recent years, actively targeted drug delivery systems have been utilized in pre-clinical studies for site-specific delivery of drugs, which reduces toxicities associated with chemotherapy. This study reports the preparation of the tumor homing ligand, transferrin (Tf) anchored methoxy-polyethylene glycol-poly(d,l-lactide) polymeric micelles (Tf-PP). Curcumin which possess wide anti-cancer activity was loaded into the micelles. Tf-PPC with average particle size of 132.16 ± 1.3 nm and encapsulation efficiency of 88...
May 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29752719/hbv-suppresses-zhx2-expression-to-promote-proliferation-of-hcc-through-mir-155-activation
#18
Xiaojia Song, Siyu Tan, Zhuanchang Wu, Leiqi Xu, Zehua Wang, Yong Xu, Tixiao Wang, Chengjiang Gao, Yaoqin Gong, Xiaohong Liang, Lifen Gao, Brett T Spear, Chunhong Ma
Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important and complex role in processes leading to HCC. We previously identified the mammalian Zinc fingers and homeoboxes 2 (ZHX2) gene as an HCC-associated tumor suppressor gene. In the present study, we investigated whether the oncogenic properties of HBV and, more specifically, HBx, involved ZHX2 silencing...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29751078/gynosaponin-tn-1-producing-from-the-enzymatic-conversion-of-gypenoside-xlvi-by-naringinase-and-its-cytotoxicity-on-hepatoma-cell-lines
#19
Yi Zheng, Zhizhong Zheng, Yanlin Ming, Mengshi Lin, Lianghua Chen, Wen Huang, Jianbo Xiao, Hetong Lin
Gypenoside XLVI (gyp XLVI) is one of the major dammarane-type triterpenoid saponins from Gynostamma pentaphallum with glucosyls at C-3 and C-20 positions, which may constrain its bioactivities. The enzymatic conversion of gyp XLVI by naringinase, and the cytotoxicity of enzymolysis product on SMMC7721 and Bel7402 hepatoma cells were investigated. The results showed that gynosaponin TN-1 (gyp TN-1) was produced from the enzymatic conversion of gyp XLVI by naringinase. The optimum enzymolysis conditions were pH 4...
May 8, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29749804/radiosensitizing-effects-of-different-size-bovine-serum-albumin-templated-gold-nanoparticles-on-h22-hepatoma-bearing-mice
#20
ShuLiang Liu, JinMei Piao, YunCai Liu, JingLong Tang, Peng Liu, DaPeng Yang, Li Zhang, Nan Ge, Zhezhen Jin, QiXiao Jiang, LianHua Cui
AIM: To evaluate intravenously injected bovine serum albumin-templated gold nanoparticles (BSA-GNPs) for radiosensitization effects on H22 hepatoma-bearing mice. MATERIALS & METHODS: BSA-GNPs in different size were injected intravenously with a dose of 4 mg Au/kg. After 30 min injection, the tumor-bearing mice were irradiated with 5 Gy x-ray. RESULTS: BSA-GNPs in 8, 50 and 187 nm were synthesized and have no obvious cytotoxicity to HeLa, HepG2 and HeCat cells when the concentration was up to 32 μM...
May 11, 2018: Nanomedicine
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