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https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#1
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 signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28198497/nested-polymerase-chain-reaction-technique-for-the-detection-of-gpc3-and-afp-mrna-in-liver-cancer-micrometastases
#2
J Luo, K Yang, Y G Wen
The incidence of liver cancer has gradually risen to a high level in China, and tumor metastasis occurs via multiple pathways. Alpha fetal protein (AFP) is the main biomarker of liver cancer micrometastases. A recent study showed that glypican-3 (GPC3), which is abundant in hepatoma cells, has promising specificity and could be used to determine the presence of malignant cells. The nested polymerase chain reaction (PCR) technique is superior in experimental sensitivity. Using rat models of liver cancer in the current study, we utilized nested PCR to detect Gpc3 and Afp mRNA to determine their relationship with liver cancer micrometastases...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28198412/a-screening-strategy-for-the-discovery-of-drugs-that-reduce-c-ebp%C3%AE-lip-translation-with-potential-calorie-restriction-mimetic-properties
#3
Mohamad A Zaini, Christine Müller, Tobias Ackermann, Jeanette Reinshagen, Gertrud Kortman, Ole Pless, Cornelis F Calkhoven
An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197637/inhibition-of-fasn-suppresses-migration-invasion-and-growth-in-hepatoma-carcinoma-cells-by-deregulating-the-hif-1%C3%AE-igfbp1-pathway
#4
Jiaojiao Gong, Shasha Shen, Yixuan Yang, Si Qin, Lifan Huang, Hongmin Zhang, Ling Chen, Yaqin Chen, Shiying Li, Sha She, Min Yang, Hong Ren, Huaidong Hu
Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Due to a high propensity to metastasize, active angiogenesis and rapid proliferation, recurrence and poor prognosis are major obstacles for treatment and cure of this disease. However, the detailed mechanisms of how fatty acid synthase (FASN) promotes migration, invasion and healing in tumor cells remain unclear. In the present study, the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples, and influenced migration, invasion of hepatoma carcinoma cells, were verified by immunohistochemistry, tissue microarrays, Transwell assay and wound healing assay...
February 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197320/synthesis-biological-evaluation-and-autophagy-mechanism-of-12n-substituted-sophoridinamines-as-novel-anticancer-agents
#5
Chongwen Bi, Na Zhang, Peng Yang, Cheng Ye, Yanxiang Wang, Tianyun Fan, Rongguang Shao, Hongbin Deng, Danqing Song
A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them, compound 6b possessing a N'-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, leukemia (K562), and breast cancer (HMLE), with IC50 between 0...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196140/hypoxia-inducible-factors-regulate-the-transcription-of-the-sprouty2-gene-and-expression-of-the-sprouty2-protein
#6
Xianlong Gao, Kristin C Hicks, Paul Neumann, Tarun B Patel
Receptor Tyrosine Kinase (RTK) signaling plays a major role in tumorigenesis and normal development. Sprouty2 (Spry2) attenuates RTK signaling and inhibits processes such as angiogenesis, cell proliferation, migration and survival, which are all upregulated in tumors. Indeed in cancers of the liver, lung, prostate and breast, Spry2 protein levels are markedly decreased correlating with poor patient prognosis and shorter survival. Thus, it is important to understand how expression of Spry2 is regulated. While prior studies have focused on the post-translation regulation of Spry2, very few studies have focused on the transcriptional regulation of SPRY2 gene...
2017: PloS One
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
#7
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/28194557/-4z-15z-octadecadienoic-acid-inhibits-glycogen-synthase-kinase-3%C3%AE-and-glucose-production-in-h4iie-cells
#8
Jun Yoshida, Shota Uesugi, Tetsuaki Kawamura, Ken-Ichi Kimura, Dawei Hu, Shuang Xia, Naoki Toyooka, Masao Ohnishi, Hideki Kawashima
Many uncommon non-methylene-interrupted fatty acids (NMI FA) are present in limpet gonads, but their biological properties remain unknown. To investigate new biological effects of naturally occurring NMI FA in eukaryotic cells, the biological activities of structurally analogous (4Z,15Z)-octadecadienoic acid (1), (9Z,20Z)-tricosadienoic acid (2), and (12Z,23Z)-hexacosadienoic acid (3) were examined by using a yeast-based drug-screening system using the Ca(2+)-sensitive mutant strain, Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)...
February 13, 2017: Lipids
https://www.readbyqxmd.com/read/28193314/celecoxib-mediated-activation-of-endoplasmic-reticulum-stress-induces-de-novo-ceramide-biosynthesis-and-apoptosis-in-hepatoma-hepg2-cells
#9
Hyo Jin Maeng, Jae-Hwi Song, Goon-Tae Kim, Yoo-Jeong Song, Kangpa Lee, Jae-Young Kim, Tae-Sik Park
Ceramides are the major sphingolipid metabolites involved in cell survival and apoptosis. When HepG2 hepatoma cells were treated with celecoxib, the expression of the genes in de novo sphingolipid biosynthesis and sphingomyelinase pathway was upregulated and cellular ceramide was elevated. In addition, celecoxib induced endoplasmic reticulum (ER) stress in a time-dependent manner. SPTLC2, a subunit of serine palmitoyltransferase, was overexpressed by adenovirus. Adenoviral overexression of SPTLC2 (AdSPTLC2) decreased cell viability of HEK293 and HepG2 cells...
February 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28192212/anti-hbv-drugs-suppress-the-growth-of-hbv-related-hepatoma-cells-via-down-regulation-of-hepatitis-b-virus-x-protein
#10
Shuqin Zhang, Shan Gao, Man Zhao, Yunxia Liu, Yanan Bu, Qiulei Jiang, Qiang Zhao, Lihong Ye, Xiaodong Zhang
Chronic infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). Meta-analyses show that adjuvant anti-HBV therapy is effective for HBV-related HCC patients in clinical. However, the significance that anti-HBV drugs depress HCC is poorly understood. Here, we investigated the effects of telbivudine (LdT), entecavir (ETV) and interferon-α2b (IFN-α2b) on HBV-related HCC. Our data showed that the treatment with the drugs significantly suppressed the growth of HBV-expressing hepatoma cells in vitro and in vivo, but failed to work in HBV-free liver cells...
February 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28190338/towards-streamlined-identification-of-dioxin-like-compounds-in-environmental-samples-through-integration-of-suspension-bioassay
#11
Hongxia Xiao, Markus Brinkmann, Beat Thalmann, Andreas Schiwy, Sigrid Große Brinkhaus, Christine Achten, Kathrin Eichbaum, Carolin Gembé, Thomas Benjamin Seiler, Henner Hollert
Effect-directed analysis (EDA) is a powerful strategy to identify biologically active compounds in environmental samples. However, in current EDA studies, fractionation and handling procedures are laborious, consist of multiple evaporation steps, and thus bear the risk of contamination and decreased recoveries of the target compounds. The low resulting throughput has been one of the major bottlenecks of EDA. Here, we propose a high-throughput EDA (HT-EDA) work-flow combining reversed phase high-performance liquid chromatography (HPLC) fractionation of samples into 96-well microplates, followed by toxicity assessment in the micro-EROD bioassay with the wild-type rat hepatoma H4IIE cells, and chemical analysis of bioactive fractions...
February 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#12
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28185215/the-apoptotic-inducible-effects-of-salicylic-acid-on-hepatoma-cell-line-relationship-with-nitric-oxide-signaling
#13
Yahui Liu, Yong Wang, Yue Hu, Shuxiong Ge, Keshi Li, Shuangshuang Wang, Li Li
Clinical and experimental data suggest that salicylic acid (SA) is tumor preventive and NO has a multitude of effects on tumor biology. Therefore, firstly, the aim of our study is to explore the important role of SA in apoptotic induction of liver cancer cells. Secondly, we investigate whether SA mediates the anti-tumor effects by NO signaling pathway. The liver cancer cell line was treated with different concentrations of SA. Cell proliferation was tested using MTS assay and cell apoptosis was assessed by flow cytometry...
February 9, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28184394/tracing-cytotoxic-effects-of-small-organic-se-species-in-human-liver-cells-back-to-total-cellular-se-and-se-metabolites
#14
T A Marschall, N Kroepfl, K B Jensen, J Bornhorst, B Meermann, D Kuehnelt, T Schwerdtle
Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species...
February 10, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28179999/cancer-stem-like-cells-can-be-induced-through-dedifferentiation-under-hypoxic-conditions-in-glioma-hepatoma-and-lung-cancer
#15
Pan Wang, Wen-Wu Wan, Shuang-Long Xiong, Hua Feng, Nan Wu
Traditional studies have shown that transcription factors, including SOX-2, OCT-4, KLF-4, Nanog and Lin-28A, contribute to the dedifferentiation and reprogramming process in normal tissues. Hypoxia is a physiological phenomenon that exists in tumors and promotes the expression of SOX-2, OCT-4, KLF-4, Nanog and Lin-28A. Therefore, an interesting question is whether hypoxia as a stimulating factor promotes the process of dedifferentiation and induces the formation of cancer stem-like cells. Studies have shown that OCT-4 and Nanog overexpression induced the formation of cancer stem cell-like cells through dedifferentiation and enhanced malignancy in lung adenocarcinoma, and reprogramming SOX-2 in pancreatic cancer cells also promoted the dedifferentiation process...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28177672/a-reappraisal-of-the-6-o-desmethylnaproxen-sulfating-activity-of-the-human-cytosolic-sulfotransferases
#16
Fatemah Alherz, Daniyah A Almarghalani, Noor A Hussein, Katsuhisa Kurogi, Ming-Cheh Liu
In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-<i>O</i>-desmethylnaproxen (<i>O</i>-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, seven, SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1, displayed <i>O</i>-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μM) together with 14 μM of the sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS)...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28177238/design-synthesis-and-biological-evaluation-of-mitochondria-targeted-flavone-naphthalimide-polyamine-conjugates-with-antimetastatic-activity
#17
Fujun Dai, Qian Li, Yuxia Wang, Chaochao Ge, Chenyang Feng, Songqiang Xie, Haoying He, Xiaojuan Xu, Chaojie Wang
Approximately 90% of cancer-associated deaths result from disseminated tumors, indicating the ineffectiveness of current therapies and the imperative need of antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide moieties was constructed by using a fragment-based drug design and a series of eight flavone-naphthalimide-polyamine conjugates were synthesized. In vitro evaluation revealed that compound 6c with a homospermidine motif displayed better cell selectivity between cancerous and normal liver cells than amonafide did...
February 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28176286/aptamer-combined-with-fluorescent-silica-nanoparticles-for-detection-of-hepatoma-cells
#18
Zixi Hu, Juntao Tan, Zongqiang Lai, Rong Zheng, Jianhong Zhong, Yiwei Wang, Xiaoxue Li, Nuo Yang, Jieping Li, Wei Yang, Yong Huang, Yongxiang Zhao, Xiaoling Lu
PURPOSE: The purpose of this study is to develop a simple, effective method to label hepatoma cells with aptamers and then detect them using fluorescent silica nanoparticles (FSNPs). METHOD: Streptavidin was conjugated to carboxyl-modified fluorescein isothiocyanate (FITC)-doped silica nanoparticles which were prepared by the reverse microemulsion method. The resulting streptavidin-conjugated fluorescent silica nanoparticles (SA-FSNPs) were mixed with hepatoma cells that had been labeled with biotin-conjugated aptamer TLS11a (Bio-TLS11a)...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28174122/role-of-salt-inducible-kinase-1-in-high-glucose-induced-lipid-accumulation-in-hepg2-cells-and-metformin-intervention
#19
Yue Zhang, Hiroshi Takemori, Chang Wang, JiaHui Fu, MingWang Xu, Liang Xiong, NingXu Li, XiuYing Wen
AIMS: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis. MAIN METHODS: A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit...
February 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28174094/recent-advances-in-hepatocellular-carcinoma-therapy
#20
REVIEW
Rinku Dutta, Ram I Mahato
Hepatocellular carcinoma (HCC), also called malignant hepatoma, is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. Incidence and mortality of HCC are increasing in Western countries and are expected to rise as a consequence of the obesity epidemic. Multiple factors trigger the initiation and progression of HCC including chronic alcohol consumption, viral hepatitis B and C infection, metabolic disorders and age. Although Sorafenib is the only FDA approved drug for the treatment of HCC, numerous treatment modalities such as transcatheter arterial chemoembolization/ transarterial chemoembolization (TACE), radiotherapy, locoregional therapy and chemotherapy have been tested in the clinics...
February 4, 2017: Pharmacology & Therapeutics
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