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https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#1
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28225186/randomised-clinical-trial-the-efficacy-and-safety-of-oltipraz-a-liver-x-receptor-alpha-inhibitory-dithiolethione-in-patients-with-non-alcoholic-fatty-liver-disease
#2
W Kim, B G Kim, J S Lee, C K Lee, J E Yeon, M S Chang, J H Kim, H Kim, S Yi, J Lee, J-Y Cho, S G Kim, J-H Lee, Y J Kim
BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study...
February 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28197211/therapeutic-effects-of-fermented-flax-seed-oil-on-nc-nga-mice-with-atopic-dermatitis-like-skin-lesions
#3
Joonhyoung Yang, Sangyeon Min, Seungug Hong
Background. Atopic Dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Objective. This experiment aimed to study the effects of Fermented Flax Seed Oil (FFSO) on symptoms such as redness, eczema, and pruritus induced by AD. Materials and Methods. AD-induced NC/Nga mice were used to observe the immunological and therapeutic effects of FFSO on skin in vivo. Raw 264.7 cells were used to investigate the effects of FFSO in cells. Fc receptor expression and concentration of beta-hexosaminidase were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28169169/drugbank-screening-revealed-alitretinoin-and-bexarotene-as-liver-x-receptor-modulators
#4
Pascal Heitel, Janosch Achenbach, Daniel Moser, Ewgenij Proschak, Daniel Merk
In silico screening of DrugBank database to detect liver X receptor (LXR) agonism of marketed drugs using a self-organizing map and successive LXR-Gal4 hybrid reporter gene assay evaluation in vitro discovered alitretinoin and bexarotene as partial liver X receptor agonists. Dose-response curves demonstrated that plasma concentrations observed in clinical trials are sufficient for LXR activation and thus could account for LXR-mediated side-effects such as hypercholesterolemia and hyperlipidemia. The discovered drugs are the first reported dual LXR/RXR agonists and can serve as lead structures for LXR and dual LXR/RXR modulator development...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28167703/a-novel-approach-to-measuring-macrophage-specific-reverse-cholesterol-transport-in-vivo-in-humans
#5
Marina Cuchel, Anna C Raper, Donna M Conlon, Daniel A Pryma, Richard H Freifelder, Rahul Poria, Debra Cromley, Xiaoyu Li, Richard L Dunbar, Benjamin French, Liming Qu, William Farver, Ching-Chiang Su, Sissel Lund-Katz, Amanda Baer, Giancomo Ruotolo, Peter Akerblad, Carol S Ryan, Lan Xiao, Todd G Kirchgessner, John S Millar, Jeffrey T Billheimer, Daniel J Rader
AIM: Reverse cholesterol transport (RCT) is thought to be an atheroprotective function of HDL, and macrophage-specific RCT in mice is inversely associated with atherosclerosis. We developed a novel method using 3H-cholesterol nanoparticles to selectively trace macrophage-specific RCT in vivo in humans. METHODS: Use of 3H-cholesterol nanoparticles was initially tested in mice to assess the distribution of tracer and response to interventions known to increase RCT...
February 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28167281/25-hydroxycholesterol-promotes-migration-and-invasion-of-lung-adenocarcinoma-cells
#6
Li Chen, Lishan Zhang, Guozhe Xian, Yinping Lv, Yanliang Lin, Yibing Wang
25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase in various organs and is involved in many processes, including lipid metabolism, inflammation and the immune response. However, the role of 25-HC in the migration and invasion of lung adenocarcinoma (ADC) cells remains largely unknown. In this study, we demonstrated that 0.1 μM 25-HC promoted ADC cell migration and invasion without affecting cell proliferation, especially after coculture with THP1-derived macrophages. Further investigation showed that 0...
February 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28167099/27-hydroxycholesterol-regulates-cholesterol-synthesis-and-transport-in-c6-glioma-cells
#7
Yu An, Dan-Di Zhang, Huan-Ling Yu, Wei-Wei Ma, Yan-Hui Lu, Quan-Ri Liu, Rong Xiao
The oxysterol 27-Hydroxycholesterol (27-OHC) is a major cholesterol metabolite that can cross the blood brain barrier (BBB) from peripheral circulation to the brain. Currently, the role of 27-OHC on cholesterol homeostasis in astrocytes and the underlying mechanisms are not defined. Since all brain cholesterol is essentially synthesized in brain itself and astrocytes as net producers of cholesterol are essential for normal brain function, here we investigated the effects of 27-OHC on cholesterol synthesis and transport in C6 glioma cells...
February 3, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28155252/the-meta-analytical-paradigm-in-an-in-silico-hybrid-pathways-and-networks-perturbed-during-exposure-to-varying-degrees-of-hypobaric-hypoxia
#8
Subhojit Paul, Kalpana Bhargava, Yasmin Ahmad
PURPOSE: Computational biology has opened a gateway to omics data analysis and shifted the focus from molecules to systemic molecular networks in the domain of hypobaric hypoxia (HH). Yet there are no meta-analytical investigations circum-venting constraints like organism (rat/human), HH exposure conditions (acute/chronic) and the tissues that can be investigated simultaneously in the realm of wet-lab experiments. EXPERIMENTAL DESIGN: We analyzed 154 DE proteins upon HH exposure using IPA tool, without the constraint of using a single organism or tissue type, to determine the most significant pathways and networks that are perturbed across a range of HH conditions RESULTS: : We found Acute phase Response Signaling, FXR/RXR Activation, LXR/RXR Activation, Clathrin-mediated endocytosis signaling, Mitochondrial Dysfunction, Production of Nitric Oxide & ROS in Macrophages and Integrin Signaling to be the most significant universally perturbed pathways...
February 2, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28147278/the-nuclear-receptor-lxr-limits-bacterial-infection-of-host-macrophages-through-a-mechanism-that-impacts-cellular-nad-metabolism
#9
Jonathan Matalonga, Estibaliz Glaria, Mariana Bresque, Carlos Escande, José María Carbó, Kerstin Kiefer, Ruben Vicente, Theresa E León, Susana Beceiro, Mónica Pascual-García, Joan Serret, Lucía Sanjurjo, Samantha Morón-Ros, Antoni Riera, Sonia Paytubi, Antonio Juarez, Fernando Sotillo, Lennart Lindbom, Carme Caelles, Maria-Rosa Sarrias, Jaime Sancho, Antonio Castrillo, Eduardo N Chini, Annabel F Valledor
Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using a model of infection by Salmonella Typhimurium, we have identified a molecular mechanism regulated by the nuclear receptor LXR that limits infection of host macrophages through transcriptional activation of the multifunctional enzyme CD38. LXR agonists reduced the intracellular levels of NAD(+) in a CD38-dependent manner, counteracting pathogen-induced changes in macrophage morphology and the distribution of the F-actin cytoskeleton and reducing the capability of non-opsonized Salmonella to infect macrophages...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#10
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
https://www.readbyqxmd.com/read/28139275/liver-x-receptor-activation-inhibits-pc-3-prostate-cancer-cells-via-the-beta-catenin-pathway
#11
Kuang Youlin, Zhang Li, He Weiyang, Kang Jian, Liang Siming, Gou Xin
BACKGROUND: Liver X receptors (LXRs) are nuclear receptors family of ligand-dependent transcription factors that play a crucial role in regulating cholesterol metabolism and inflammation. Recent studies show that LXR agonists exhibit anti-cancer activities in a variety of cancer cell lines including prostate. To further identify the potential mechanisms of LXRα activation on prostate cancer, we investigated the effect of LXR agonist T0901317 on PC3 prostate cancer cell and in which activity of beta-catenin pathway involved...
May 12, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28119310/activation-of-liver-x-receptors-promotes-inflammatory-cytokine-mrna-degradation-by-upregulation-of-tristetraprolin
#12
Ji Xiao, Quan Chen, Dan Tang, Weiwei Ou, Jiazheng Wang, Zhongcheng Mo, Chaoke Tang, Liangyu Peng, Deming Wang
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFα mRNA degradation. Moreover, T0901317 destabilized TNFα mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay...
January 23, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28097086/liver-x-receptor-agonist-t0901317-reverses-resistance-of-a549-human-lung-cancer-cells-to-egfr-tki-treatment
#13
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/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
#14
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
#15
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/28086800/relevance-of-fxr-p62-sqstm1-pathway-for-survival-and-protection-of-mouse-hepatocytes-and-liver-especially-with-steatosis
#16
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/28076928/rxr%C3%AE-is-upregulated-in-first-trimester-endometrial-glands-of-spontaneous-abortions-unlike-lxr-and-ppar%C3%AE
#17
J Knabl, A Vattai, R Hüttenbrenner, S Hutter, M Karsten, U Jeschke
Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analysed for expression of the nuclear receptors LXR, RXRα and PPARγ...
November 2, 2016: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28070626/nuclear-receptors-regulate-lipid-metabolism-and-oxidative-stress-markers-in-chondrocytes
#18
Anusha Ratneswaran, Margaret Man-Ger Sun, Holly Dupuis, Cynthia Sawyez, Nica Borradaile, Frank Beier
: Joint homeostasis failure can result in osteoarthritis (OA). Currently, there are no treatments to alter disease progression in OA, but targeting early changes in cellular behavior has great potential. Recent data show that nuclear receptors contribute to the pathogenesis of OA and could be viable therapeutic targets, but their molecular mechanisms in cartilage are incompletely understood. This study examines global changes in gene expression after treatment with agonists for four nuclear receptor implicated in OA (LXR, PPARδ, PPARγ, and RXR)...
January 9, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28067791/ligands-of-therapeutic-utility-for-the-liver-x-receptors
#19
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/28057729/lxr%C3%AE-and-lxr%C3%AE-nuclear-receptors-evolved-in-the-common-ancestor-of-gnathostomes
#20
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
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