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https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#1
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29149103/human-hepatocyte-transplantation-for-liver-disease-current-status-and-future-perspectives
#2
REVIEW
Valeria Iansante, Ragai R Mitry, Céline Filippi, Emer Fitzpatrick, Anil Dhawan
Liver transplantation is the accepted treatment for patients with acute liver failure and liver-based metabolic disorders. However, donor organ shortage and lifelong need for immunosuppression are the main limitations to liver transplantation. In addition, loss of the native liver as target organ for future gene therapy for metabolic disorders limits the futuristic treatment options, resulting in the need for alternative therapeutic strategies. A potential alternative to liver transplantation is allogeneic hepatocyte transplantation...
November 14, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29148584/metabolic-effects-of-p-p-dde-on-atlantic-salmon-hepatocytes
#3
Pål A Olsvik, Liv Søfteland
Decades after being banned in many countries, DDT and its metabolites are still considered major environmental hazards. The p,p'-DDE isomer, the DDT metabolite found in highest concentration in aquaculture feeds, is an endocrine disruptor with demonstrated ability to induce epigenetic effects. This study aimed at examining the impact of p,p'-DDE on Atlantic salmon. Primary hepatocytes were exposed to four concentrations of p,p'-DDE (0.1, 1, 10, 100 μm) for 48 hours, and endpoints included cytotoxicity, global DNA methylation, targeted transcription and metabolomics profiling (100 μm)...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#4
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29145424/levosimendan-protects-human-hepatocytes-from-ischemia-reperfusion-injury
#5
Stefanie N Brunner, Nicolai V Bogert, Andreas A Schnitzbauer, Eva Juengel, Anton Moritz, Isabella Werner, Angela Kornberger, Andres Beiras-Fernandez
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes. METHODS: Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions...
2017: PloS One
https://www.readbyqxmd.com/read/29145157/bmscs-derived-mir-223-containing-exosomes-contribute-to-liver-protection-in-experimental-autoimmune-hepatitis
#6
Lu Chen, Feng-Bin Lu, Da-Zhi Chen, Jin-Lu Wu, En-de Hu, Lan-Man Xu, Ming-Hua Zheng, Hui Li, Yu Huang, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29145152/possible-role-of-arthrospira-platensis-in-reversing-oxidative-stress-mediated-liver-damage-in-rats-exposed-to-lead
#7
Samah R Khalil, Walaa M Elhady, Yaser H A Elewa, Noura E Abd El-Hameed, Sozan A Ali
Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis; SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA; as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days)...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29145026/lc-ms-ms-quantification-of-felinine-metabolites-in-tissues-fluids-and-excretions-from-the-domestic-cat-felis-catus
#8
Ayami Futsuta, Wataru Hojo, Tamako Miyazaki, Tetsuro Yamashita, Masao Miyazaki
Domestic cat urine contains large concentrations of the unusual amino acid, felinine (2-amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid). A felinine derivative, 3-mercapt-3-methylbutanol is a potential scent signal for letting other animals know that the scent owners are cats. 3-Methylbutanol-glutathione (MBG) is an upstream precursor of the biosynthetic pathway of felinine that may be produced in hepatocytes by conjugation of glutathione with isopentenyl pyrophosphate, an intermediate for cholesterol biosynthesis...
November 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29144590/metabolic-profiling-of-normal-hepatocyte-and-hepatocellular-carcinoma-cells-via-1-h-nuclear-magnetic-resonance-spectroscopy
#9
Yang Chen, Zhong Chen, Jiang-Hua Feng, Yun-Bin Chen, Nai-Shun Liao, Ying Su, Chang-Yan Zou
Hepatocellular carcinoma (HCC) causes death mainly by disseminated metastasis progression from the organ being confined. Different metastatic stages are closely related to cellular metabolic profiles. Normal hepatocyte and HepG2 cell line from low metastatic HCC were studied by NMR-based metabolomic techniques. Multivariate and univariate statistical analyses were utilized to identify characteristic metabolites from cells and cultured media. Elevated levels of acetate, creatine, isoleucine, leucine, and phenylalanine were observed in HepG2 cells, suggesting more active in gathering nutrient components along with altered amino acid metabolisms and enhanced lipid metabolism...
November 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29144397/sulforaphane-alters-%C3%AE-naphthoflavone-induced-changes-in-activity-and-expression-of-drug-metabolizing-enzymes-in-rat-hepatocytes
#10
Kateřina Lněničková, Andrea Dymáková, Barbora Szotáková, Iva Boušová
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer...
November 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143555/qualitative-and-quantitative-prediction-of-human-in-vivo-metabolic-pathways-in-a-human-hepatocyte-murine-stromal-cell-co-culture-model
#11
Kenneth C Cassidy, Ping Yi
1. This study assessed the value of a static in vitro human hepatocyte-murine stromal cell co-culture model to qualitatively and quantitatively predict human in vivo metabolic clearance pathways using (14)C-labeled test compounds and compared these results to an in vitro suspended human hepatocyte model and the in vivo human (14)C ADME studies. 2. Test compounds represented a diverse set of clearance pathways (Phase I and Phase II). Compounds were incubated for 4 h in suspended human hepatocytes and for 24 and 168 h in the human co-culture model...
November 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29143438/protective-effects-of-coenzyme-q10-nanoparticles-on-dichlorvos-induced-hepatotoxicity-and-mitochondrial-lysosomal-injury
#12
Aziz Eftekhari, Elham Ahmadian, Aida Azami, Mohammad Johari-Ahar, Mohammad Ali Eghbal
Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM)...
November 16, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29142472/prostaglandin-e1-protects-hepatocytes-against-endoplasmic-reticulum-stress-induced-apoptosis-via-protein-kinase-a-dependent-induction-of-glucose-regulated-protein-78-expression
#13
Fang-Wan Yang, Yu Fu, Ying Li, Yi-Huai He, Mao-Yuan Mu, Qi-Chuan Liu, Jun Long, Shi-De Lin
AIM: To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS: Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29142176/evaluation-of-the-human-relevance-of-the-constitutive-androstane-receptor-mediated-mode-of-action-for-rat-hepatocellular-tumor-formation-by-the-synthetic-pyrethroid-momfluorothrin
#14
Yu Okuda, Masahiko Kushida, Hiroko Kikumoto, Yoshimasa Nakamura, Hashihiro Higuchi, Satoshi Kawamura, Samuel M Cohen, Brian G Lake, Tomoya Yamada
High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29141998/vanillic-acid-attenuates-obesity-via-activation-of-the-ampk-pathway-and-thermogenic-factors-in-vivo-and-in-vitro
#15
Yunu Jung, Jinbong Park, Hye-Lin Kim, Jung-Eun Sim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Woong Mo Yang, Seok-Geun Lee, Kwang Seok Ahn, Jae-Young Um
Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#16
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#17
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29141157/the-devastating-effect-of-exposure-to-high-irradiation-dose-on-liver-and-the-performance-of-synthesized-nano-hap-in-relieve-the-associated-symptoms-in-rats
#18
Eman Ismail Gheriany, Sameh A Awwad
Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction by a mechanism involving oxidative stress. The present investigation was undertaken to study the possible therapeutic effect of nano-HAp on whole body gamma irradiation induced hepatotoxicity in rats. The study consisted of three groups of 10 rats each. Group 1 (control), whereas group 2 received a single dose of γ-radiation (10Gy). The animals in groups 3 was treated with nano-HAp (100 mg/kg b.w.) once / week for three weeks starting in the next day of γ radiation...
November 15, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29141109/hepatic-ppar%C3%AE-mediates-the-major-metabolic-effects-of-wy-14643
#19
Guolin Li, Chad N Brocker, Cen Xie, Tingting Yan, Audrey Noguchi, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez
BACKGROUND AND AIM: Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue-specific functions of PPARα remain to be elucidated. This study aimed to explore the tissue-specific functions of PPARα in response to Wy-14643. METHODS: A hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with the potent PPARα agonist Wy-14643...
November 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29140985/notch-signaling-and-progenitor-ductular-reaction-in-steatohepatitis
#20
Carola M Morell, Romina Fiorotto, Marica Meroni, Aileen Raizner, Barbara Torsello, Massimiliano Cadamuro, Gaia Spagnuolo, Eleanna Kaffe, Salvatore Sutti, Emanuele Albano, Mario Strazzabosco
BACKGROUND AND OBJECTIVE: Persistent hepatic progenitor cells (HPC) activation resulting in ductular reaction (DR) is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis...
2017: PloS One
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