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https://www.readbyqxmd.com/read/28816564/cytotoxicity-screening-and-cytokine-profiling-of-nineteen-nanomaterials-enables-hazard-ranking-and-grouping-based-on-inflammogenic-potential
#1
Kunal Bhattacharya, Gözde Kiliç, Pedro M Costa, Bengt Fadeel
Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free...
August 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28812343/xanthohumol-suppresses-mylip-idol-gene-expression-and-modulates-ldlr-abundance-and-activity-in-hepg2-cells
#2
Shih-Fen Chen, Pei-Yi Chen, Hao-Jen Hsu, Ming-Jiuan Wu, Jui-Hung Yen
Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as anti-atherosclerosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 μM) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 ± 2.1% to 115.0±1.3% and 135.2±2.7%, and enhanced the LDL uptake activity from 100...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28810520/studies-on-the-regulation-of-lipid-metabolism-and-the-mechanism-of-the-aqueous-and-ethanol-extracts-of-usnea
#3
Jiali Zhu, Xuemei Zhang, Xiu Chen, Yong Sun, Yaolan Dai, Chang Chen, Tiane Zhang, Zhiyong Yan
OBJECTIVES: Usnea is a lichen of Usnea diffracta Vain and Usnea longissima Ach, which belongs to the genus Usnea Adans of Usneaceae. Usnea exerts numerous pharmacological activities, while its lipid regulatory activities remain unreported. This study aims to evaluate the effects of aqueous and ethanol extracts of Usnea on the regulation of lipid metabolism and to explore the possible mechanism. METHODS: Hyperlipidemia rat model was established by feeding with high-fat diet for 45days...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhance-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#4
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28798155/ifn-%C3%AE-aggravates-neointimal-hyperplasia-by-inducing-endoplasmic-reticulum-stress-and-apoptosis-in-macrophages-by-promoting-ubiquitin-dependent-liver-x-receptor-%C3%AE-degradation
#5
Qiang Zhao, Dong Zhou, Hongjun You, Bowen Lou, Yan Zhang, Yuling Tian, Ning Guo, Xiaoli Chen, Yan Liu, Yue Wu, Zuyi Yuan, Juan Zhou
Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN-γ and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN-γ significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-γ-treated macrophages...
August 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28797077/gender-difference-in-nash-susceptibility-roles-of-hepatocyte-ikk%C3%AE-and-sult1e1
#6
Noriko Matsushita, Mohamed T Hassanein, Marcos Martinez-Clemente, Raul Lazaro, Samuel W French, Wen Xie, Keane Lai, Michael Karin, Hidekazu Tsukamoto
Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice...
2017: PloS One
https://www.readbyqxmd.com/read/28794002/klf4-regulation-of-ch25h-and-lxr-mitigates-atherosclerosis-susceptibility
#7
Zhao Li, Marcy Martin, Jin Zhang, Hsi-Yuan Huang, Liang Bai, Jiao Zhang, Jian Kang, Ming He, Jie Li, Mano R Maurya, Shakti Gupta, Guangjin Zhou, Panjamaporn Sangwung, Yong-Jiang Xu, Ting Lei, Hsien-Da Huang, Mohit Jain, Mukesh K Jain, Shankar Subramaniam, John Y-J Shyy
Background -Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of sterol regulatory element binding protein 2 (SREBP2), 25-hydroxycholesterol (25-HC) and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages...
August 9, 2017: Circulation
https://www.readbyqxmd.com/read/28792854/phytosterols-synergize-with-endotoxin-to-augment-inflammation-in-kupffer-cells-but-alone-have-limited-direct-effect-on-hepatocytes
#8
Gregory Guthrie, Bryan Tackett, Barbara Stoll, Camilia Martin, Oluyinka Olutoye, Douglas G Burrin
INTRODUCTION: Phytosterols are implicated in the development of parenteral nutrition-associated liver disease. A newly proposed mechanism for phytosterol-mediated parenteral nutrition-associated liver disease is through phytosterol-facilitated hepatic proinflammatory cytokine release following exposure to intestinally derived bacteria. Whether the proinflammatory effects are liver cell specific is not known. AIM: To determine if phytosterols cause inflammation in hepatocytes or Kupffer cells independently or require costimulation by lipopolysaccharide (LPS)...
August 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28790455/the-transcription-factor-mafb-promotes-anti-inflammatory-m2-polarization-and-cholesterol-efflux-in-macrophages
#9
Hwijin Kim
Macrophages play pivotal roles in the progression and regression of atherosclerosis. Accumulating evidence suggests that macrophage polarization into an anti-inflammatory M2 state is a key characteristic of atherosclerotic plaques undergoing regression. However, the molecular mechanisms underlying this potential association of the M2 polarization with atherosclerosis regression remain poorly understood. Further, human genetic factors that facilitate these anti-atherogenic processes remain largely unknown. We report that the transcription factor MafB plays pivotal roles in promoting macrophage M2 polarization...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790326/intestinal-toxicity-of-the-type-b-trichothecene-mycotoxin-fusarenon-x-whole-transcriptome-profiling-reveals-new-signaling-pathways
#10
Imourana Alassane-Kpembi, Juliana Rubira Gerez, Anne-Marie Cossalter, Manon Neves, Joëlle Laffitte, Claire Naylies, Yannick Lippi, Martine Kolf-Clauw, Ana Paula L Bracarense, Philippe Pinton, Isabelle P Oswald
The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774737/the-mechanism-of-diabetic-retinopathy-pathogenesis-unifying-key-lipid-regulators-sirtuin-1-and-liver-x-receptor
#11
Sandra S Hammer, Eleni Beli, Nermin Kady, Qi Wang, Kiana Wood, Todd A Lydic, Goldis Malek, Daniel R Saban, Xiaoxin X Wang, Sugata Hazra, Moshe Levi, Julia V Busik, Maria B Grant
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28767424/induction-of-socs3-by-liver-x-receptor-suppresses-the-proliferation-of-hepatocellular-carcinoma-cells
#12
Haojun Xiong, Yan Zhang, Shan Chen, Zhenhong Ni, Jintao He, Xinzhe Li, Bo Li, Kai Zhao, Fan Yang, Yijun Zeng, Bingbo Chen, Fengtian He
Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765952/mtor-signaling-promotes-foam-cell-formation-and-inhibits-foam-cell-egress-through-suppressing-the-sirt1-signaling-pathway
#13
Haixiang Zheng, Yucai Fu, Yusheng Huang, Xinde Zheng, Wei Yu, Wei Wang
Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28760992/specific-regulation-of-thermosensitive-lipid-droplet-fusion-by-a-nuclear-hormone-receptor-pathway
#14
Shiwei Li, Qi Li, Yuanyuan Kong, Shuang Wu, Qingpo Cui, Mingming Zhang, Shaobing O Zhang
Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760679/amelioration-of-amyloid-%C3%AE-induced-retinal-inflammatory-responses-by-a-lxr-agonist-to901317-is-associated-with-inhibition-of-the-nf-%C3%AE%C2%BAb-signaling-and-nlrp3-inflammasome
#15
Chunyan Lei, Ru Lin, Jiaming Wang, Lifei Tao, Xinyu Fu, Yiguo Qiu, Bo Lei
Amyloid β (Aβ) is a pathogenic peptide associated with many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The retinal inflammation in response to Aβ is implicated in the pathogenesis of several ocular diseases including age-related macular degeneration, Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found that a single intravitreal injection of oligomeric Aβ1-40 in mouse activated the NLRP3 inflammasome and the NF-κB signaling, induced the production of inflammatory cytokines including TNF-α and IL-6...
July 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28760623/pregnane-x-receptor-pxr-signaling-in-seabream-primary-hepatocytes-exposed-to-extracts-of-seawater-samples-collected-from-polycyclic-aromatic-hydrocarbons-pahs-contaminated-coastal-areas
#16
Paolo Cocci, Gilberto Mosconi, Francesco Alessandro Palermo
Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants damaging to the marine environment and the wildlife. Herein, we investigated the effects of extracts from coastal seawaters (central Adriatic sea, Italy), showing high concentrations of PAHs, on pregnane X receptor (PXR)-transcriptional regulation of the cytochrome P450 3A (CYP3A) gene using seabream primary hepatocytes. The results show that concentrated extracts of seawater with original ΣPAH concentrations above the putative threshold of 30 ng L(-1) increased expression of PXR and its main target gene, CYP3A...
July 19, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/28745211/the-lipid-lowering-effects-and-associated-mechanisms-of-dietary-phytosterol-supplementation
#17
Jerad H Dumolt, Todd C Rideout
Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation...
July 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28741954/side-chain-modified-ergosterol-and-stigmasterol-derivatives-as-liver-x-receptor-agonists
#18
Maura Marinozzi, Francisco Fermin Castro Navas, Daniela Maggioni, Emanuele Carosati, Giovanni Bocci, Maria Carloncelli, Gianluca Giorgi, Gabriele Cruciani, Raffaella Fontana, Vincenzo Russo
A series of stigmasterol and ergosterol derivatives, characterized by the presence of oxygenated functions at C-22 and/or C-23 positions, were designed as potential liver X receptor (LXR) agonists. The absolute configuration of the newly created chiral centers was definitively assigned for all the corresponding compounds. Among the 16 synthesized compounds, 21, 27, and 28 were found to be selective LXRα agonists, whereas 20, 22, and 25 showed good selectivity for the LXRβ isoform. In particular, 25 showed the same degree of potency as 22R-HC (3) at LXRβ, while it was virtually inactive at LXRα (EC50 = 14...
July 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#19
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28739689/lxr-activation-down-regulates-lipid-raft-markers-flot2-and-dhhc5-in-mcf-7-breast-cancer-cells
#20
Delphine Carbonnelle, Trang H Luu, Chloe Chaillou, Jean-Michel Huvelin, Jean-Marie Bard, Hassan Nazih
BACKGROUND/AIM: Lipid rafts are cholesterol-enriched microdomains of the plasma membrane. Recent studies have underlined that their integrity is critical for cancer cell survival. Liver X receptor (LXR) has a central role in cellular cholesterol homeostasis and its stimulation inhibits proliferation of several cancer cell lines. This study investigated whether LXR could modulate lipid rafts integrity and consequently alter proliferation of the MCF-7 breast cancer cell line. MATERIALS AND METHODS: Effect of LXR agonist T0901317 on integrity of MCF-7 lipid rafts was examined by studying the expression of rafts marker flotillin-2 (FLOT2) and DHHC5, which palmitoylates FLOT2, and by studying the expression of phospho-Akt...
August 2017: Anticancer Research
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