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Liver X Receptor

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https://www.readbyqxmd.com/read/29663407/ground-beef-high-in-total-fat-and-saturated-fatty-acids-decreases-x-receptor-signaling-targets-in-peripheral-blood-mononuclear-cells-of-men-and-women
#1
Seong H Choi, Ghazal Gharahmany, Rosemary L Walzem, Thomas H Meade, Stephen B Smith
We hypothesized that consumption of saturated fatty acids in the form of high-fat ground beef for 5 weeks would depress liver X receptor signaling targets in peripheral blood mononuclear cells (PBMC) and that changes in gene expression would be associated with the corresponding changes in lipoprotein cholesterol (C) concentrations. Older men (n = 5, age 68.0 ± 4.6 years) and postmenopausal women (n = 7, age 60.9 ± 3.1 years) were assigned randomly to consume ground-beef containing 18% total fat (18F) or 25% total fat (25F), five patties per week for 5 weeks with an intervening 4-week washout period...
April 16, 2018: Lipids
https://www.readbyqxmd.com/read/29660500/occurrence-and-seasonal-variation-of-equine-estrogens-equilin-and-equilenin-in-the-river-water-of-japan-implication-with-endocrine-disrupting-potentials-to-japanese-medaka-oryzias-latipes
#2
Hiroshi Ishibashi, Masaya Uchida, Keisuke Yoshimoto, Yuta Imamura, Ryoko Yamamoto, Yoshinori Ikenaka, Masahito Kawai, Nobuhiro Ichikawa, Yuji Takao, Nobuaki Tominaga, Yasuhiro Ishibashi, Koji Arizono
In this study, we determined the concentration of equine estrogens, such as equilin (Eq) and equilenin (Eqn), in the river water collected from nine research stations in Hokkaido, Japan. The LC-MS/MS analysis revealed that Eq concentrations were 2.7 ± 6.7, 0.22 ± 0.12, and 1.2 ± 0.64 ng/L in Sep 2015, Feb 2016, and Jul 2016, respectively. Eqn had concentration levels similar to those of Eq. Comparison of the concentrations at nine research stations showed that seasonal variation was observed in the detected Eq and Eqn concentration levels...
April 13, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29660435/yangonin-protects-against-cholestasis-and-hepatotoxity-via-activation-of-farnesoid-x-receptor-in-vivo-and-in-vitro
#3
Xiaoguang Gao, Ting Fu, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Xiaokui Huo, Xiaobo Yang, Ming Zou, Qiang Meng
Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic strategy against cholestasis. The purpose of the current study is to screen novel FXR agonists and verify the anti-cholestasis effect of yangonin in vivo and in vitro. The computational strategy of two-dimensional virtual screening was used to search for new FXR agonists, and dual-luciferase reporter gene assay was used to further demonstrate FXR activation by yangonin...
April 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29658330/comparative-cytotoxicity-and-apoptotic-pathways-induced-by-nanosilver-in-human-liver-hepg2-and-l02-cells
#4
Y Xue, J Wang, Y Huang, X Gao, L Kong, T Zhang, M Tang
Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20-160 μg mL-1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29655695/alisma-orientale-extract-exerts-the-reversing-cholestasis-effect-by-activation-of-farnesoid-x-receptor
#5
Xiao-Kui Huo, Jing Liu, Zhen-Long Yu, Yi-Fei Wang, Chao Wang, Xiang-Ge Tian, Jing Ning, Lei Feng, Cheng-Peng Sun, Bao-Jing Zhang, Xiao-Chi Ma
BACKGROUND: Cholestasis is a clinical syndrome of liver damage that is caused by accumulation of bile acids in the liver and systemic circulation. Farnesoid X receptor (FXR) can regulate synthesis, metabolism, and excretion of bile acids. The rhizomes of Alisma orientale is a well-known traditional Chinese medicine to treat edema, obesity, gonorrhea, leukorrhea, diarrhea, hyperlipidemia, and diabetes in China. HYPOTHESIS/PURPOSE: We hypothesized Alisma orientale extract (AOE) to exert hepatoprotective effect against α-naphthylisothiocyanate (ANIT) induced cholestasis in rat...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29650790/effect-of-endocannabinoid-oleamide-on-rat-and-human-liver-cytochrome-p450-enzymes-in-in-vitro-and-in-vivo-models
#6
Gabriela Dovrtelova, Ondrej Zendulka, Kristyna Noskova, Jan Jurica, Ondrej Pes, Jan Dusek, Alejandro Carazo, Iveta Zapletalova, Natasa Hlavacova, Petr Pavek
The endocannabinoid system is important for many physiological and pathological processes, but its role in the regulation of liver cytochromes P450 (CYPs) is still unknown. We studied the influence of the endocannabinoid oleamide on rat and human liver CYPs. Oleamide was administered i.p. to rats at doses of 0.1, 1 and 10 mg/kg/day for 7 days. The content and activity of key CYPs was evaluated in rat liver microsomes. Moreover, its interactions with nuclear receptors regulating CYP genes and serum levels of their ligands (prolactin, corticosterone, and free triiodothyronine) were tested in vitro CYP inhibition assays...
April 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29649907/farnesoid-x-receptor-modulators-2014-present-a-patent-review
#7
Valentina Sepe, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
The nuclear receptor FXR regulates the expression of genes involved in bile acids, glucose and lipid homeostasis. For its role as guardian of metabolism, FXR has been identified a promising pharmacological target in liver bile acid and lipid accumulation, such as cholestasis and non-alcoholic fatty liver disease (NAFLD). The field of FXR research is extremely competitive with a large number of patents and articles published in the last decades identifying promising hit compounds. Areas covered. The present review summarizes recent patent activity (2014-to date) filing for synthetic and natural FXR ligands, including bile acid derivatives and non-steroidal compounds, alongside their in vitro and in vivo efficacy as well as their therapeutic applications...
April 13, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29643920/mir-33-inhibition-attenuates-the-effect-of-liver-x-receptor-agonist-t0901317-on-expression-of-liver-x-receptor-alpha-in-mice-liver
#8
Abbas Mohammadi, Hossein Fallah, Beydolah Shahouzehi, Hamid Najafipour
BACKGROUND: microRNAs play pivotal roles in metabolism and other aspects of cell biology. microRNA-33 and liver X receptor (LXR) affect lipid metabolism and cholesterol trafficking. In this study, we evaluated effects of co-administration of miR-33 inhibitor and LXR activator on LXR-α and adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression in mice liver. METHODS: Twenty-four mice were randomly allocated into four groups (n = 6). Group 1 mice received standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour LXR agonist (T0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids (LNA) anti-miR-33 and group 4 received both T0901317 and in vivo LNA anti-miR-33...
November 2017: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/29643332/macrophage-derived-il-1%C3%AE-nf-%C3%AE%C2%BAb-signaling-mediates-parenteral-nutrition-associated-cholestasis
#9
Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah McKenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol
In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC...
April 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29627981/discovery-of-a-novel-small-molecule-modulator-of-c-x-c-chemokine-receptor-type-7-as-a-treatment-for-cardiac-fibrosis
#10
Elnaz Menhaji-Klotz, Kevin D Hesp, Allyn Timothy Londregan, Amit S Kalgutkar, David W Piotrowski, Markus Boehm, Kun Song, Tim Ryder, Kevin Beaumont, Rhys M Jones, Karen Atkinson, Janice A Brown, John Litchfield, Jun Xiao, Daniel P Canterbury, Kristen Burford, Benjamin A Thuma, Chris Limberakis, Wenhua Jiao, Scott W Bagley, Saket Agarwal, Danielle Crowell, Stephen Pazdziorko, Jessica Ward, David A Price, Valerie Clerin
C-X-C chemokine receptor type 7 (CXCR7) is involved in cardiac and immune pathophysiology. We report the discovery of a novel 1,4-diazepine CXCR7 modulator, demonstrating for the first time, the role of pharmacological CXCR7 intervention in cardiac repair. Structure-activity relationship (SAR) studies demonstrated that a net reduction in lipophilicity (logD) and incorporation of saturated ring systems yielded compounds with good CXCR7 potency and improvements in oxidative metabolic stability in human liver microsomes (HLM)...
April 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29627574/exosomes-secreted-by-placental-stem-cells-selectively-inhibit-growth-of-aggressive-prostate-cancer-cells
#11
Taylor C Peak, Prakash Praharaj, Gati K Panigrahi, Michael Doyle, Yixin Su, Isabel R Schlaepfer, Ravi Singh, Donald J Vander Griend, Julie Alickson, Ashok Hemal, Anthony Atala, Gagan Deep
The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSCExo ) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5...
April 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29626480/tspa-as-a-novel-atf6%C3%AE-translocation-inducer-efficiently-ameliorates-insulin-sensitivity-restoration-and-glucose-homeostasis-in-db-db-mice
#12
Tingting Zhou, Yanhua Cheng, Wenzhong Yan, Xiaofan Shi, Xin Xu, Jinpei Zhou, Jian Li, Jing Chen, Xu Shen
Activating transcription factor 6α (ATF6α) as a transducer in unfolded protein response (UPR), plays an important role in liver glucose metabolism and insulin resistance. Thus, targeting ATF6α activation has been proposed to be a potential strategy for anti-T2DM drug discovery. Here, we determined that small molecule 2-[5-[1-(4-chlorophenoxy)ethyl]-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide (TSPA) functioned as an ATF6α translocation inducer effectively promoting ATF6α translocation into nucleus and ameliorating glucose homeostasis on db/db mice...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29622007/synergistic-effect-of-phytochemicals-on-cholesterol-metabolism-and-lipid-accumulation-in-hepg2-cells
#13
Ennian Leng, Yuan Xiao, Zhentao Mo, Yiqi Li, Yueyue Zhang, Xiaosi Deng, Min Zhou, Chaochao Zhou, Zengxuan He, Jingyi He, Lu Xiao, Junming Li, Wenna Li
BACKGROUND: Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells)...
April 5, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29615898/antihyperalgesic-properties-of-honokiol-in-inflammatory-pain-models-by-targeting-of-nf-%C3%AE%C2%BAb-and-nrf2-signaling
#14
Sidra Khalid, Muhammad Z Ullah, Ashraf U Khan, Ruqayya Afridi, Hina Rasheed, Adnan Khan, Hussain Ali, Yeong S Kim, Salman Khan
The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis , in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29614969/27-hydroxycholesterol-increases-%C3%AE-synuclein-protein-levels-through-proteasomal-inhibition-in-human-dopaminergic-neurons
#15
Jared Schommer, Gurdeep Marwarha, Trevor Schommer, Travis Flick, Jonah Lund, Othman Ghribi
BACKGROUND: Accumulation of the α-synuclein (α-syn) protein is a hallmark of a group of brain disorders collectively known as synucleinopathies. The mechanisms responsible for α-syn accumulation are not well understood. Several studies suggest a link between synucleinopathies and the cholesterol metabolite 27-hydroxycholesterol (27-OHC). 27-OHC is the major cholesterol metabolite in the blood that crosses the blood brain barrier, and its levels can increase following hypercholesterolemia, aging, and oxidative stress, which are all factors for increased synucleinopathy risk...
April 3, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29608331/rsjp40-protein-promotes-ppar%C3%AE-expression-in-lx-2-cells-through-microrna-27b
#16
Dandan Zhu, Lei Lyu, Pei Shen, Jianxin Wang, Jinling Chen, Xiaolei Sun, Liuting Chen, Li Zhang, Qi Zhou, Yinong Duan
miR-27b is reported to participate in the proliferation and differentiation of hepatic stellate cells (HSCs) and to regulate fat metabolism of rat HSCs by targeting retinoid X receptor α. Our previous study also indicated that the recombinant P40 protein from Schistosoma japonicum (rSjP40) inhibited the activation of HSCs. In this study, we observed the expression of miR-27b in rSjP40-treated LX-2 cells and explored its potential mechanisms. Quantitative real-time PCR showed that rSjP40 inhibits the expression of miR-27b in LX-2 cells...
April 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29606873/noninvasive-evaluation-of-the-migration-effect-of-transplanted-endothelial-progenitor-cells-in-ischemic-muscle-using-a-multimodal-imaging-agent
#17
Xingui Peng, Cong Li, Yingying Bai, Xinyi Wang, Yi Zhang, Yanli An, Gao-Jun Teng, Shenghong Ju
Background: Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. However, the survival, migration and therapeutic efficacy of EPCs after transplantation need to be better understood for further cell therapy. Purpose: This study investigated the migration effect of EPCs labeled with a multimodal imaging agent in a murine ischemic hindlimb model, using magnetic resonance imaging (MRI) and optical imaging after transplantation. Methods: EPCs derived from mouse bone marrow were labeled with a multimodal imaging agent and were administered through intracardiac delivery to mice with ischemic hindlimbs...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29603355/apoptotic-cells-trigger-the-abca1-stat6-pathway-leading-to-ppar-%C3%AE-expression-and-activation-in-macrophages
#18
Myeong-Joo Kim, Ye-Ji Lee, Young-So Yoon, Minsuk Kim, Ji Ha Choi, Hee-Sun Kim, Jihee Lee Kang
The signal transducer and activator of transcription 6 (STAT6) transcription factor activates peroxisome proliferator-activated receptor gamma (PPAR-γ)-regulated gene expression in immune cells. We investigated proximal membrane signaling that was initiated in macrophages after exposure to apoptotic cells that led to enhanced PPAR-γ expression and activity, using specific siRNAs for ABCA1, STAT6, and PPAR-γ, or their antagonists. The interactions between mouse bone marrow-derived macrophages or RAW 264.7 cells and apoptotic Jurkat cells, but not viable cells, resulted in the induction of STAT6 phosphorylation as well as PPAR-γ expression and activation...
March 30, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29593532/-epigallocatechin-3-gallate-ameliorates-atherosclerosis-and-modulates-hepatic-lipid-metabolic-gene-expression-in-apolipoprotein-e-knockout-mice-involvement-of-ttc39b
#19
Li-Long Pan, Yan Wu, Ru-Qing Wang, Jin-Wu Chen, Jing Chen, Yan Zhang, Ya-Jun Chen, Ming Geng, Zhong-Dong Xu, Min Dai, Jin-Hua Li, Wei Wang, Zheng-Zhu Zhang
Background: Aberrant chronic inflammation and excess accumulation of lipids play a pivotal role in the occurrence and progression of atherosclerosis. (-)-Epigallocatechin-3-gallate (EGCG), the major catechins in green tea, displayed anti-atherosclerotic properties in vivo and in vitro . However, the effects and underlying mechanism of EGCG on atherosclerosis remain unclear. Methods: Male apolipoprotein E-knockout (ApoE-/- ) mice (7 weeks old) fed with high-fat diet (HFD) were treated with normal saline or EGCG (40 mg/kg/d, i...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29590657/angiotensin-ii-suppresses-rev-erb%C3%AE-expression-in-thp-1-macrophages-via-the-ang-ii-type-1-receptor-liver-x-receptor-%C3%AE-pathway
#20
Shipeng Wang, Xia Gu, Qi Zhang, Xiling Zhang, Yilan Li, Yuan Yao, Bo Yu, Yao Zhang
BACKGROUND/AIMS: Angiotensin II (Ang II) regulates the expression of some core clock genes; excess Ang II leads to atherosclerosis advancement. Macrophage Rev-erbα mediates clockwork and inflammation, and plays a role in atherosclerotic lesion progression. However, the role of Ang II in regulating Rev-erbα expression in macrophages remains unclarified. METHODS: We induced THP-1 macrophages by phorbol 12-myristate 13-acetate and investigated the effect of Ang II on Rev-erbα expression via real-time polymerase chain reaction, western blotting and small interfering RNA (siRNA) techniques...
March 22, 2018: Cellular Physiology and Biochemistry
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