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Liver X Receptor

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https://www.readbyqxmd.com/read/28097086/liver-x-receptor-agonist-t0901317-reverses-resistance-of-a549-human-lung-cancer-cells-to-egfr-tki-treatment
#1
Haixia Cao, Shaorong Yu, Dan Chen, Changwen Jing, Zhuo Wang, Rong Ma, Siwen Liu, Jie Ni, Jifeng Feng, Jianzhong Wu
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective in lung cancer patients carrying sensitive EGFR mutations. In this study, we investigated if liver X receptor (LXR) agonist T0901317 could reverse the resistance of lung cancer cell lines A549 and H1650 to EGFR-TKI treatment. We found that T0901317 could make natural EGFR-TKI-resistant A549 human lung cancer cells sensitive to EGFR-TKI treatment and that this was dependent on LXRβ expression. However, T0901317 does not have a similar effect on another natural EGFR-TKI-resistant cell line H1650...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28092182/an-estrogen-receptor-%C3%AE-selective-agonist-inhibits-non-alcoholic-steatohepatitis-in-preclinical-models-by-regulating-bile-acid-and-xenobiotic-receptors
#2
Suriyan Ponnusamy, Quynh T Tran, Thirumagal Thiyagarajan, Duane D Miller, Dave Bridges, Ramesh Narayanan
Non-alcoholic steatohepatitis (NASH) affects 8-10 million people in the US and up to 75% of obese individuals. Despite this, there are no approved oral therapeutics to treat NASH and therefore the need for novel approaches exists. The estrogen receptor β (ER-β)-selective agonist, β-LGND2, inhibits body weight and white adipose tissue, and increases metabolism, resulting in higher energy expenditure and thermogenesis. Due to favorable effects of β-LGND2 on obesity, we hypothesized that β-LGND2 will prevent NASH directly by reducing lipid accumulation in the liver or indirectly by favorably changing body composition...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28091828/liver-x-receptor-%C3%AE-lxr%C3%AE-promoted-invasion-and-emt-of-gastric-cancer-cells-by-regulation-of-nf-%C3%AE%C2%BAb-activity
#3
Linhua Ji, Bin Zhang, Gang Zhao
Aberrant expression of Liver X receptor α (LXRα) has been frequently reported in various types of cancers excluding gastric cancer (GC). Moreover, the role of LXRα in human GC has not been previously reported. In this study, we investigated the effect of LXRα down-regulation on invasion and EMT of GC. The expression of LXRα in GC cell lines was detected by real-time PCR. The LXRα siRNA was transiently transfected into GC cells using Lipofectamine™ 2000 reagent. Subsequently, cell invasive ability was evaluated by Transwell assays...
January 16, 2017: Human Cell
https://www.readbyqxmd.com/read/28091615/pirfenidone-controls-the-feedback-loop-of-the-at1r-p38-mapk-renin-angiotensin-system-axis-by-regulating-liver-x-receptor-%C3%AE-in-myocardial-infarction-induced-cardiac-fibrosis
#4
Chunmei Li, Rui Han, Le Kang, Jianping Wang, Yonglin Gao, Yanshen Li, Jie He, Jingwei Tian
Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087808/identification-of-a-novel-liver-x-receptor-agonist-that-regulates-the-expression-of-key-cholesterol-homeostasis-genes-with-distinct-pharmacological-characteristics
#5
Ni Li, Xiao Wang, Yanni Xu, Yuan Lin, Ningyu Zhu, Peng Liu, Duo Lu, Shuyi Si
Activation of Liver X receptor (LXR) is associated with cholesterol metabolism and anti-inflammatory processes, which makes beneficial to anti-atherosclerosis. Nevertheless, existing agonists which target LXR, for example TO901317, are related to unwanted side-effects. In the present study, using a screening method we identified IMB-808, which displayed potent dual LXRα/β agonistic activity. In vitro, IMB-808 effectively increased the expressing quantity of genes related to reverse cholesterol transport process as well as those associated with cholesterol metabolism pathway in multiple cell lines...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28086803/compendium-of-tcdd-mediated-transcriptomic-response-datasets-in-mammalian-model-systems
#6
Stephenie D Prokopec, Kathleen E Houlahan, Ren X Sun, John D Watson, Cindy Q Yao, Jamie Lee, Christine P'ng, Renee Pang, Alexander H Wu, Lauren C Chong, Ashley B Smith, Nicholas J Harding, Ivy D Moffat, Jere Lindén, Sanna Lensu, Allan B Okey, Raimo Pohjanvirta, Paul C Boutros
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28086800/relevance-of-fxr-p62-sqstm1-pathway-for-survival-and-protection-of-mouse-hepatocytes-and-liver-especially-with-steatosis
#7
Sanae Haga, Yimin, Michitaka Ozaki
BACKGROUND: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological conditions. Surgically, severe liver injury after surgical resection often leads to fatal liver failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the injury of hepatocytes and liver is a serious concern in various clinical settings. METHODS: We studied the effects of the farnesoid X receptor (FXR) on cell survival and steatosis in mouse hepatocytes (AML12 mouse liver cells) and investigated their molecular mechanisms...
January 13, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28067791/ligands-of-therapeutic-utility-for-the-liver-x-receptors
#8
REVIEW
Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar, Kevin E Riley, Guangdi Wang
Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism...
January 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28063306/constitutive-expression-and-activity-of-cytochrome-p450-in-conventional-pigs
#9
Søren Drud Nielsen, Yvonne Bauhaus, Galia Zamaratskaia, Matheus Antunes Junqueira, Karoline Blaabjerg, Bjørn Petrat-Melin, Jette Feveile Young, Martin Krøyer Rasmussen
Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent events, like drug metabolism. However, comprehensive knowledge about the constitutive expression of the major CYP and corresponding transcription factors is limited. We compared the constitutive mRNA expression of aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor and CYP1A1, CYP1A2, CYP2A, CYP2E1 and CYP3A in liver, adipose tissue, muscle and small intestine in pigs, as well as the expression along the length of the small intestine and colon...
December 23, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/28063004/tubulin-alpha-8-is-expressed-in-hepatic-stellate-cells-and-is-induced-in-transformed-hepatocytes
#10
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Thomas S Weiss, Sabrina Krautbauer, Christa Buechler
Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28060747/25-hydroxycholesterol-is-involved-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#11
Sung-Min Kim, Min-Young Noh, Heejaung Kim, So-Young Cheon, Kang Mi Lee, Jaeick Lee, Eunju Cha, Kyung Seok Park, Kwang-Woo Lee, Jung-Joon Sung, Seung Hyun Kim
This study aimed to evaluate the levels of three major hydroxycholesterols (24-, 25-, and 27-hydroxycholesterols) in the serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), as well as to show their role in the pathogenesis of ALS experimental models. The level of 25-hydroxycholesterol were higher in untreated ALS patients (n = 30) than in controls without ALS (n = 33) and ALS patients treated with riluzole (n = 9) both in their serum and CSF. The level of 25-hydroxycholesterol in the serum of ALS patients were significantly associated with their disease severity and rate of progression...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058446/hepatotoxic-effects-of-cyproconazole-and-prochloraz-in-wild-type-and-hcar-hpxr-mice
#12
Philip Marx-Stoelting, Katrin Ganzenberg, Constanze Knebel, Flavia Schmidt, Svenja Rieke, Helen Hammer, Felix Schmidt, Oliver Pötz, Michael Schwarz, Albert Braeuning
The agricultural fungicides cyproconazole and prochloraz exhibit hepatotoxicity in rodent studies and are tumorigenic following chronic exposure. Both substances are suspected to act via a CAR (constitutive androstane receptor)/PXR (pregnane-X-receptor)-dependent mechanism. Human relevance of these findings is under debate. A 28-day toxicity study was conducted in mice with humanized CAR and PXR (hCAR/hPXR) with two dose levels (50 or 500 ppm) of both substances, using the model CAR activator phenobarbital as a reference...
January 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28057729/lxr%C3%AE-and-lxr%C3%AE-nuclear-receptors-evolved-in-the-common-ancestor-of-gnathostomes
#13
Elza Fonseca, Raquel Ruivo, Mónica Lopes-Marques, Huixian Zhang, Miguel M Santos, Byrappa Venkatesh, L Filipe C Castro
Nuclear receptors (NRs) regulate numerous aspects of the endocrine system. They mediate endogenous and exogenous cues, ensuring a homeostatic control of development and metabolism. Gene duplication, loss and mutation have shaped the repertoire and function of NRs in metazoans. Here we examine the evolution of a pivotal orchestrator of cholesterol metabolism in vertebrates, the liver X receptors (LXRs). Previous studies suggested that LXRα and LXRβ genes emerged in the mammalian ancestor. However, we show through genome analysis and functional assay that bona fide LXRα and LXRβ orthologues are present in reptiles, coelacanth and chondrichthyans but not in cyclostomes...
January 4, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28056322/-the-therapeutic-value-and-safety-of-icotinib-as-first-line-therapy-for-advanced-non-small-cell-lung-cancer-patients
#14
H Chen, H P Wang, L Zhang, X Y Si
Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48...
January 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28052875/liver-x-receptor-%C3%AE-lxr%C3%AE-increases-aqp2-protein-level-via-a-post-transcriptional-mechanism-in-renal-collecting-ducts
#15
Wen Su, Shi-Zheng Huang, Min Gao, Xiao-Mu Kong, Jan-Ake Gustafsson, Su-Juan Xu, Bing Wang, Feng Zheng, Li-Hong Chen, Nan-Ping Wang, You-Fei Guan, Xiao-Yan Zhang
Liver X Receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ-/- mice exhibited a reduced response to dDAVP stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28045080/transforming-growth-factor-%C3%AE-activated-kinase-1-transcriptionally-suppresses-hepatitis-b-virus-replication
#16
Jinke Pang, Geng Zhang, Yong Lin, Zhanglian Xie, Hongyan Liu, Libo Tang, Mengji Lu, Ran Yan, Haitao Guo, Jian Sun, Jinlin Hou, Xiaoyong Zhang
Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28041731/analysis-of-bull-bos-taurus-seminal-vesicle-fluid-proteome-in-relation-to-seminal-plasma-proteome
#17
B Westfalewicz, M A Dietrich, A Mostek, A Partyka, W Bielas, W Niżański, A Ciereszko
The existing knowledge on the bull seminal vesicle proteome, a major seminal plasma constituent, and its relationship with seminal plasma is limited. This knowledge is prerequisite for a better understanding of seminal plasma variability, which is linked to semen quality. The objective of this study was to characterize the proteomes of seminal vesicle fluid and seminal plasma and to compare them to better understand the origin of seminal plasma proteins. We collected ejaculates and seminal vesicle fluid postmortem from 6 mature Holstein Friesian bulls...
December 29, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/28038938/regulation-of-the-expression-of-lxr-in-rat-hypothalamic-and-hippocampal-explants
#18
María Sol Kruse, Lucas Gabriel Suarez, Héctor Coirini
Liver X receptors (LXR) are important transcription factors involved in the regulation of carbohydrate and lipid metabolism and are expressed in different brain areas. Recently we described that LXR expression in the hypothalamus is sensitive to serum levels of lipids and carbohydrates. Here, we further characterized the effects of glucose, insulin, cholesterol and cholic acid on the expression of LXRα and LXRβ in hypothalamus and hippocampus explants as in vitro models. The LXR activation products, GLUT2 and ABCA1, were also analyzed by Western blot...
December 27, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28035356/effect-of-yi-guan-jian-decoction-on-differentiation-of-bone-marrow-mesenchymalstem-cells-into-hepatocyte-like-cells-in-dimethylnitrosamine-induced-liver-cirrhosis-in-mice
#19
Yan Xiang, Bing-Yao Pang, Yuan Zhang, Qiao-Ling Xie, Ying Zhu, Ai-Jing Leng, Long-Qing Lu, Hai-Long Chen
Yi Guan Jian decoction (YGD) may induce the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells (HLCs); however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate this process. To do this, a dimethylnitrosamine (DMN)-induced liver cirrhosis mouse model was established. The mice from the model group were randomly divided into three subgroups: i) Negative control, ii) hepatocyte growth factor and iii) YGD. The overall health, liver function and histological alterations were monitored...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28034800/effects-of-tetramethylpyrazine-from-chinese-black-vinegar-on-antioxidant-and-hypolipidemia-activities-in-hepg2-cells
#20
Jicheng Chen, Jingjing Tian, Huifang Ge, Ruihai Liu, Jianbo Xiao
Tetramethylpyrazine is a bioactive compound found in Chinese black vinegar. This work is to investigate the potential effects of tetramethylpyrazine on intracellular cholesterol modulation in HepG2 cells. The results demonstrated that tetramethylpyrazine can induce intracellular cholesterol efflux. Tetramethylpyrazine may also improve endothelial function through its antioxidant effects by inhibiting reactive oxygen species levels and increasing the antioxidant enzymes superoxide dismutase and catalase. Tetramethylpyrazine increased liver X receptor and peroxisome proliferator-activated receptor gene expression in HepG2 cells...
December 26, 2016: Food and Chemical Toxicology
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