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https://www.readbyqxmd.com/read/29161501/phenanthrene-induced-apoptosis-and-its-underlying-mechanism
#1
Xiangsheng Hong, Jianhui Qin, Rui Chen, Lilai Yuan, Jinmiao Zha, Chao Huang, Na Li, Xiaoya Ji, Zijian Wang
Phenanthrene (Phe) is one of the most abundant low-molecular-weight polycyclic aromatic hydrocarbons (PAHs). Widespread human and aquatic organism exposure to Phe has been reported, but the toxic effects of Phe and potential mechanisms are unclear. We focused on the chronic hepatotoxicity of Phe in adult Chinese rare minnows (Gobiocypris rarus) and the underlying mechanisms. The chronic effects of exposing Chinese rare minnows to 8.9, 82.3, or 510.0 μg/L Phe for 30 days were examined by histopathological observation, TUNEL assays, caspase activity assays, and gene expression profiles...
November 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29159818/c-ebp%C3%AE-dependent-pre-neoplastic-tumor-foci-are-the-origin-of-hepatocellular-carcinoma-and-aggressive-pediatric-liver-cancer
#2
Ashley Cast, Leila Valanejad, Mary Wright, Phuong Nguyen, Anita Gupta, Liqin Zhu, Soona Shin, Nikolai Timchenko
Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes; while hepatocellular carcinoma (HCC) is caused by the de-differentiation of hepatocytes into Cancer Stem Cells (CSCs). However, the mechanisms of aggressive HBL and mechanisms that cause de-differentiation of hepatocytes into CSCs are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of de-differentiation of hepatocytes into CSCs...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29159681/advanced-strategies-for-eliminating-the-cccdna-of-hbv
#3
REVIEW
Jingwu Dong, Jie Ying, Xiaoyan Qiu, Yu Lu, Miaomiao Zhang
Persistent hepatitis B virus (HBV) infection of hepatocytes is associated with a covalently closed circular DNA (cccDNA) episome. Although serologic hepatitis B surface antigen tests are negative, the presence of cccDNA is obviously increased in HBeAg-positive patients compared with that in HBeAg-negative patients, inactive carriers and patients. Moreover, trace cccDNA levels can also be found in the liver cells of patients with resolved hepatitis B infections. Therefore, clearance of cccDNA in hepatocytes could be an effective cure for HBV...
November 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29159225/data-on-the-effect-of-mir-15b-on-the-expression-of-insr-in-murine-c2c12-myocytes
#4
Won-Mo Yang, Kyung-Ho Min, Se-Whan Park, Wan Lee
The ectopic expression of miR-15b is linked causally to impaired insulin signaling in human HepG2 hepatocytes through the suppression of INSR (Yang et al., 2015) [1]. In this data article, we further examined the effect of miR-15b on insulin signaling in a murine skeletal muscle cells, C2C12 myocytes. Although the 3'UTR of mouse INSR mRNA has an appropriate binding site for miR-15b based on TargetScan analysis, the ectopic expression of miR-15b did not suppress the expression and insulin-stimulated phosphorylation of insulin signaling intermediates in C2C12 myocytes...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29159216/data-on-the-decreased-expression-of-foxo1-by-mir-1271-in-hepg2-hepatocytes
#5
Won-Mo Yang, Kyung-Ho Min, Se-Whan Park, Wan Lee
Obesity and metabolic diseases are closely associated with insulin resistance. Obesity-induced miRNAs are also considered to be potential contributors to the development of insulin resistance and type 2 diabetes. Previously, the expression of miR-1271 was reported to be upregulated in the liver of diet-induced obese mice (Yang et al., 2016) [1]. In this data article, multiple in silico analysis predicted FOXO1 gene to be a direct target of miR-1271. Dual luciferase reporter gene analysis showed that miR-1271 suppressed FOXO1 expression by direct binding to 3'UTR...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29159212/data-on-the-expression-of-pepck-in-hepg2-hepatocytes-transfected-with-mir-195
#6
Won-Mo Yang, Kyung-Ho Min, Se-Whan Park, Wan Lee
Dietary fats rich in saturated fatty acid (SFA) increase the risk of metabolic diseases, and certain microRNAs (miRNAs) dysregulated by SFA are associated with the pathogenesis of insulin resistance and type 2 diabetes. A previous study found that miR-195 is increased by SFA and impairs hepatic insulin signaling through the suppression of INSR (Yang et al., 2014) [1]. This article reports accompanying data to determine the effect of miR-195 on the expression of PEPCK, a key player in hepatic gluconeogenesis...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29159202/a-humoral-immune-response-alters-the-distribution-of-enzyme-replacement-therapy-in-murine-mucopolysaccharidosis-type-i
#7
Steven Q Le, Shih-Hsin Kan, Don Clarke, Valentina Sanghez, Martin Egeland, Kristen N Vondrak, Terence M Doherty, Moin U Vera, Michelina Iacovino, Jonathan D Cooper, Mark S Sands, Patricia I Dickson
Antibodies against recombinant proteins can significantly reduce their effectiveness in unanticipated ways. We evaluated the humoral response of mice with the lysosomal storage disease mucopolysaccharidosis type I treated with weekly intravenous recombinant human alpha-l-iduronidase (rhIDU). Unlike patients, the majority of whom develop antibodies to recombinant human alpha-l-iduronidase, only approximately half of the treated mice developed antibodies against recombinant human alpha-l-iduronidase and levels were low...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29159133/integration-of-novel-approaches-demonstrates-simultaneous-metabolic-inactivation-and-car-mediated-hepatocarcinogenesis-of-a-nitrification-inhibitor
#8
Jessica L LaRocca, Reza J Rasoulpour, B Bhaskar Gollapudi, David L Eisenbrandt, Lynea A Murphy, Matthew J LeBaron
Nitrapyrin, a nitrification inhibitor, produces liver tumors in mice at high doses. Several experiments were performed to investigate molecular, cellular, and apical endpoints to define the key events leading to the tumor formation. These data support a mode-of-action (MoA) characterized by constitutive androstane receptor (CAR) nuclear receptor activation, increased hepatocellular proliferation leading to hepatocellular foci and tumor formation. Specifically, nitrapyrin induced a dose-related increase in the Cyp2b10/CAR-associated transcript and protein...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#9
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29158523/treatment-of-myocardial-infarction-with-gene-modified-mesenchymal-stem-cells-in-a-small-molecular-hydrogel
#10
Zhiye Wu, Guoqin Chen, Jianwu Zhang, Yongquan Hua, Jinliang Li, Bei Liu, Anqing Huang, Hekai Li, Minsheng Chen, Caiwen Ou
The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxia in vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only group in vitro and in vivo...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158401/kinesin-dependent-mechanism-for-controlling-triglyceride-secretion-from-the-liver
#11
Priyanka Rai, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S Kamat, Roop Mallik
Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158183/serine-prevented-high-fat-diet-induced-oxidative-stress-by-activating-ampk-and-epigenetically-modulating-the-expression-of-glutathione-synthesis-related-genes
#12
Xihong Zhou, Liuqin He, Shengnan Zuo, Yumei Zhang, Dan Wan, Ciming Long, Pan Huang, Canrong Wu, Xin Wu, Gang Liu, Yulong Yin
Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57BL/6J mice (9week-old) were randomly assigned into four groups (n=10) and fed: i) a low-fat diet; ii) a low-fat diet supplemented with 1% (wt:vol) serine; iii) a high-fat (HF) diet; and iv) a HF diet supplemented with 1% serine, respectively...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29158088/interplay-of-adipocyte-and-hepatocyte-leptin-upregulates-hepcidin
#13
Kiyoko Yamamoto, Takahiro Kuragano, Tomoko Kimura, Masayoshi Nanami, Yukiko Hasuike, Takeshi Nakanishi
Conflicting evidence concerning leptin, an adipocyte-derived hormone, in atherogenesis and non-alcoholic fatty liver disease (NAFLD) has been reported. Iron metabolism and iron-mediated oxidative stress should be taken into consideration for the clarification of the pathogenesis of these diseases. In this study, we demonstrate that leptin receptor activation directly affects iron metabolism by the finding that serum levels of hepcidin, the master regulator of iron in the whole body, were significantly lower in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29158052/baicalin-attenuates-non-alcoholic-steatohepatitis-by-suppressing-key-regulators-of-lipid-metabolism-inflammation-and-fibrosis-in-mice
#14
Junli Zhang, Haiming Zhang, Xiaoling Deng, Ning Zhang, Beibei Liu, Shengliang Xin, Guixin Li, Keshu Xu
AIMS: Baicalin (BA), an active flavonoid compound originating from the herb of Scutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis. MAIN METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4weeks...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29157977/cell-type-specific-pharmacological-kinase-inhibition-for-cancer-chemoprevention
#15
Manjeet Deshmukh, Shigeki Nakagawa, Takaaki Higashi, Adam Vincek, Anu Venkatesh, Marina Ruiz de Galarreta, Anna P Koh, Nicolas Goossens, Hadassa Hirschfield, C Billie Bian, Naoto Fujiwara, Atsushi Ono, Hiroki Hoshida, Mohamed El-Abtah, Noor B Ahmad, Amaia Lujambio, Roberto Sanchez, Bryan C Fuchs, Klaas Poelstra, Jai Prakash, Yujin Hoshida
Safety is prerequisite for preventive medicine, but non-toxic agents are generally ineffective as clinical chemoprevention. Here we propose a strategy overcoming this challenge by delivering molecular-targeted agent specifically to the effector cell type to achieve sufficient potency, while circumventing toxicity in the context of cancer chemoprevention. Hepatic myofibroblasts drive progressive fibrosis that results in cirrhosis and liver cancer. In a rat model of cirrhosis-driven liver cancer, a small molecule epidermal growth factor receptor inhibitor, erlotinib, was delivered specifically to myofibroblasts by a versatile nanoparticle-based system, targeting platelet-derived growth factor receptor-beta uniquely expressed on their surface in the liver...
November 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29157685/recent-advances-in-the-discovery-of-small-molecule-c-met-kinase-inhibitors
#16
REVIEW
Palak K Parikh, Manjunath D Ghate
c-Met is a prototype member of a subfamily of heterodimeric receptor tyrosine kinases (RTKs) and is the receptor for hepatocyte growth factor (HGF). Binding of HGF to its receptor c-Met, initiates a wide range of cellular signalling, including those involved in proliferation, motility, migration and invasion. Importantly, dysregulated HGF/c-Met signalling is a driving factor for numerous malignancies and promotes tumour growth, invasion, dissemination and/or angiogenesis. Dysregulated HGF/c-Met signalling has also been associated with poor clinical outcomes and resistance acquisition to some approved targeted therapies...
August 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29157602/induction-of-fibroblast-growth-factor-21-does-not-require-activation-of-the-hepatic-x-box-binding-protein-1-in-mice
#17
Shantel Olivares, Anne S Henkel
OBJECTIVE: Fibroblast growth factor 21 (FGF21), a key regulator of the metabolic response to fasting, is highly induced by endoplasmic reticulum (ER) stress. The X-box binding protein 1 (Xbp1) is one of several ER stress proteins that has been shown to directly activate the FGF21 promoter. We aimed to determine whether hepatic Xbp1 is required for induction of hepatic FGF21 in vivo. METHODS: Mice bearing a hepatocyte-specific deletion of Xbp1 (Xbp1(LKO)) were subjected to fasting, pharmacologic ER stress, or a ketogenic diet, all potent stimuli of Fgf21 expression...
December 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29157299/the-similarities-between-smdcs-and-regdcs-in-alleviating-the-immune-injury-caused-by-transplantation-of-hepatocytes-differentiated-from-escs
#18
Cheng Zhang, Wenwei Liao, Bing Cai, Furong Liu, Qiong Ke, Xiaofeng Zhu, Xiaoshun He, Anbin Hu
BACKGROUND: This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs. METHODS: Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro...
November 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29156995/combined-repeated-dose-and-reproductive-developmental-toxicity-screening-test-of-benzene-1-1-oxybis-tetrapropylene-derivs-in-rats
#19
Yasuhiro Tsubokura, Ryuichi Hasegawa, Sunao Aso, Toshio Kobayashi, Takayuki Koga, Satsuki Hoshuyama, Yutaka Oshima, Katsumi Miyata, Yuji Kusune, Takako Muroi, Naoki Hashizume, Yoshiyuki Inoue, Shozo Ajimi, Kotaro Furukawa
We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000 mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42-53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods...
November 20, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29156799/asiatic-acid-protects-against-hepatic-ischemia-reperfusion-injury-by-inactivation-of-kupffer-cells-via-ppar%C3%AE-nlrp3-inflammasome-signaling-pathway
#20
Ying Xu, Jun Yao, Chen Zou, Heng Zhang, Shouliang Zhang, Jun Liu, Gui Ma, Pengcheng Jiang, Wenbo Zhang
Hepatic ischemia/reperfusion (I/R) contributes to major complications in clinical practice affecting perioperative morbidity and mortality. Recent evidence suggests the key role of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammaosme activation on the pathogenesis of I/R injury. Asiatic acid (AA) is a pentacyclic triterpene derivative presented with versatile activities, including antioxidant, anti-inflammation and hepatoprotective effects. This study was designed to determine whether AA had potential hepatoprotective benefits against hepatic I/R injury, as well as to unveil the underlying mechanisms involved in the putative effects...
October 17, 2017: Oncotarget
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