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Lipid mediators

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https://www.readbyqxmd.com/read/28651330/rosiglitazone-improves-insulin-resistance-mediated-by-10-12-conjugated-linoleic-acid-in-a-male-mouse-model-of-metabolic-syndrome
#1
Shari Wang, Leela Goodspeed, Katherine E Turk, Barbara Houston, Laura J den Hartigh
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high fat high sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling PPARγ antagonism. Since thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28651232/silymarin-prevents-nlrp3-inflammasome-activation-and-protects-against-intracerebral-hemorrhage
#2
Raorao Yuan, Hengyi Fan, Shiqi Cheng, WeiWei Gao, Xin Xu, Shigang Lv, Minhua Ye, Miaojing Wu, Xingen Zhu, Yan Zhang
Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28650998/functional-annotation-of-alzheimer-s-disease-associated-loci-revealed-by-gwass
#3
Zengpeng Han, Han Huang, Yue Gao, Qingyang Huang
Genome-wide association studies (GWASs) discovered a number of SNPs and genes associated with Alzheimer's disease (AD). However, how these SNPs and genes influence the liability to AD is not fully understood. We deployed computational approaches to explore the function and action mechanisms of AD -related SNPs and genes identified by GWASs, including the effects of 195 GWAS lead SNPs and 338 proxy SNPs on miRNAs binding and protein phosphorylation, their RegulomeDB and 3DSNP scores, and gene ontology, pathway enrichment and protein-protein interaction network of 126 AD-associated genes...
2017: PloS One
https://www.readbyqxmd.com/read/28650667/gender-specific-association-between-fgfr4-gly388arg-gene-variants-and-hypertension
#4
Nasser M Al-Daghri, Abdul Khader Mohammed, Omar S Al-Attas, Hossam M Draz, Majed S Alokail
AIMS: Variations in fibroblast growth factor (FGF) levels have been associated with alterations in blood pressure. FGFs mediate their function through binding to their FGF receptor (FGFR). FGFR4 Gly388Arg polymorphism is associated with cancer and cardiovascular diseases, but its association with hypertension is unclear. Here, we aimed to investigate the association between FGFR4 Gly388Arg polymorphism and hypertension. MATERIALS AND METHODS: Three hundred Saudi individuals (150 normotensive controls and 150 hypertensive subjects) were genotyped for FGFR4 Gly388Arg (G/A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method...
June 26, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28650666/labile-incorporation-of-cholesterol-terminated-poly-acrylic-acid-for-the-facile-surface-modification-of-lipid-vesicles
#5
Sang-Min Lee
An amphiphilic cholesterol-terminated poly[acrylic acid] (Chol-PAA) that can be self-aggregated into nanoscale micelles in aqueous media has been prepared via nitroxide-mediated radical polymerization for the facile postformation modification of lipid vesicles. By varying the amount of Chol-PAA addition, the incorporation of Chol-PAA on the liposome templates was verified with zeta potential while the dynamic light scattering measurements revealed the polymer length of Chol-PAA dictated the hydrodynamic diameter of the resulting polymer-grafted vesicles (PGVs)...
June 26, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28650048/cooperative-wrapping-of-nanoparticles-of-various-sizes-and-shapes-by-lipid-membranes
#6
Kai Xiong, Jiayin Zhao, Daowen Yang, Qingwen Cheng, Jiuling Wang, Hongbing Ji
Understanding the interaction between nanoparticles (NPs) and cell membranes is crucial for the design of NP-based drug delivery systems and for the assessment of the risks exerted by the NPs. Recent experimental and theoretical studies have shown that cell membranes can mediate attraction between NPs and form tubular structures to wrap multiple NPs. However, the cooperative wrapping process is still not well understood, and the shape effect of NPs is not considered. In this article, we use large-scale coarse-grained molecular dynamics (CGMD) simulations to study the cooperative wrapping of NPs when a varying number of NPs adhered to the membrane...
June 26, 2017: Soft Matter
https://www.readbyqxmd.com/read/28649842/lipo-oligomer-nanoformulations-for-targeted-intracellular-protein-delivery
#7
Peng Zhang, Benjamin Steinborn, Ulrich Lächelt, Stefan Zahler, Ernst Wagner
Here, we report novel lipo-oligoaminoamide nanoformulations for targeted intracellular protein delivery. Formulations are generated by first bioreversibly conjugating a sequence-defined amphiphilic lipo-oligomer 728 to the cargo protein via disulfide bonds, followed by formulation of the formed 728-SS-protein conjugate with different helper lipids in various compositions. The triblock oligoaminoamide 728 contains cysteines for reversible covalent protein conjugation and crosslink-stabilization of formed nanoparticles, polyethylene glycol (PEG) for shielding and providing a hydrophilic domain, eight cationizable succinoyl tetraethylene pentamine (Stp) repeats for endosomal buffering and escape into the cytosol, and a tetra-oleic acid block for hydrophobic stabilization...
June 26, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28649260/tomato-udp-glucose-sterol-glycosyltransferases-a-family-of-developmental-and-stress-regulated-genes-that-encode-cytosolic-and-membrane-associated-forms-of-the-enzyme
#8
Karla Ramirez-Estrada, Nídia Castillo, Juan A Lara, Monserrat Arró, Albert Boronat, Albert Ferrer, Teresa Altabella
Sterol glycosyltransferases (SGTs) catalyze the glycosylation of the free hydroxyl group at C-3 position of sterols to produce sterol glycosides. Glycosylated sterols and free sterols are primarily located in cell membranes where in combination with other membrane-bound lipids play a key role in modulating their properties and functioning. In contrast to most plant species, those of the genus Solanum contain very high levels of glycosylated sterols, which in the case of tomato may account for more than 85% of the total sterol content...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28649014/apatite-nanoparticles-strongly-improve-red-blood-cell-cryopreservation-by-mediating-trehalose-delivery-via-enhanced-membrane-permeation
#9
Martin Stefanic, Kevin Ward, Harvey Tawfik, Ralf Seemann, Vladimir Baulin, Yachong Guo, Jean-Baptiste Fleury, Christophe Drouet
Cryopreservation of red blood cells (RBC) is an important method for maintaining an inventory of rare RBC units and managing special transfusion circumstances. Currently, in a clinical setting, glycerol is used as cryoprotectant against freezing damage. After thawing and before transfusion, glycerol must however be removed to avoid intravascular hemolysis, via a complex and time-consuming deglycerolization process which requires specialized equipment. Improved cryopreservation methods using non-toxic agents are required to increase biocompatibility and decrease processing time...
June 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28649002/cpla2%C3%AE-activates-pi3k-akt-and-inhibits-smad2-3-during-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells
#10
Hui Fu, Yuchao He, Lisha Qi, Lu Chen, Yi Luo, Liwei Chen, Yongmei Li, Ning Zhang, Hua Guo
Cytosolic phospholipase A2α (cPLA2α), a key phospholipase that regulates lipid metabolism, plays an important role in tumor progression. In the present study of hepatocellular carcinoma (HCC), cPLA2α was overexpressed in highly metastatic HCC cell lines. Immunohistochemical staining showed increased levels of cPLA2α at the invasive edges of HCC, and a clinicopathological analysis of samples from 111 patients revealed that its expression level was linked with micro-vascular invasion and cirrhosis. Knockdown of cPLA2α inhibited migration, probably due to its role in actin polymerization...
June 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28648817/modulatory-effect-of-silymarin-on-nuclear-factor-erythroid-2-related-factor-2-regulated-redox-status-nuclear-factor-%C3%AE%C2%BAb-mediated-inflammation-and-apoptosis-in-experimental-gastric-ulcer
#11
Walaa Arafa Keshk, Samer Mahmoud Zahran, Mohamed Alaa Katary, Darin Abd El Aziz Ali
Non-steroidal anti-inflammatory drugs (NSAIDs) consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Silymarin (SM) is a flavonoid mixture with anti-oxidant and anti-inflammatory activities which explain its protective role against hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus we went further to investigate the potential protective effects of SM against indomethacin-induced gastric injury in rats. Pretreatment with SM (50 mg/kg orally) attenuated the severity of gastric mucosal damage as evidenced by decreasing ulcer index (UI) and ulcer score, improvement of disturbed histopathologicl features to be insignificant with those induced by the reference anti-ulcer drug...
June 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28648660/friction-mediates-scission-of-tubular-membranes-scaffolded-by-bar-proteins
#12
Mijo Simunovic, Jean-Baptiste Manneville, Henri-François Renard, Emma Evergren, Krishnan Raghunathan, Dhiraj Bhatia, Anne K Kenworthy, Gregory A Voth, Jacques Prost, Harvey T McMahon, Ludger Johannes, Patricia Bassereau, Andrew Callan-Jones
Membrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis...
June 21, 2017: Cell
https://www.readbyqxmd.com/read/28648584/control-of-lipid-droplet-fusion-and-growth-by-cide-family-proteins
#13
REVIEW
Guangang Gao, Feng-Jung Chen, Linkang Zhou, Lu Su, Dijin Xu, Li Xu, Peng Li
Cell death-inducing DFF45-like effector (CIDE) family proteins including Cidea, Cideb and Cidec/Fsp27 are expressed in many different tissues and are known as lipid droplet (LD)-and ER-associated proteins. Systematic analyses using genetically modified animal models have demonstrated that CIDE proteins play important roles in regulating various aspects of lipid homeostasis, including lipid storage, lipolysis and lipid secretion. Recent research in ours and other laboratories has revealed that CIDE proteins are crucial regulators of LD fusion and growth in the adipose tissue, liver, skin and mammary glands...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#14
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647324/ampk-as-a-therapeutic-target-for-treating-metabolic-diseases
#15
REVIEW
Emily A Day, Rebecca J Ford, Gregory R Steinberg
The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation...
June 21, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28647061/vesicle-fusion-mediated-by-solanesol-anchored-dna
#16
Kristina M Flavier, Steven G Boxer
Fusion between two lipid bilayers is one of the central processes in cell biology, playing a key role in endocytosis, exocytosis, and vesicle transport. We have previously developed a model system that uses the hybridization of complementary DNA strands to model the formation of the SNARE four-helix bundle that mediates synaptic vesicle fusion and used it to study vesicle fusion to a tethered lipid bilayer. Using single vesicle assays, 70% of observed fusion events in the DNA-lipid system are arrested at the hemifusion stage, whereas only 5% eventually go to full fusion...
June 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28647025/olumacostat-glasaretil-a-promising-topical-sebum-suppressing-agent-that-affects-all-major-pathogenic-factors-of-acne-vulgaris
#17
Bodo C Melnik
Hunt et al. show that olumacostat glasaretil, an inhibitor of acetyl coenzyme A carboxylase, reduces saturated and monounsaturated fatty acyl chains in sebaceous lipids. Topical olumacostat glasaretil application decreases hamster ear sebaceous gland size and shows efficacy in treating patients with acne vulgaris. Olumacostat glasaretil-mediated sebum suppression may reduce Propionibacterium acnes growth and biofilm formation, comedogenesis, and inflammation.
July 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646803/effects-of-balneotherapy-on-serum-levels-of-shingosine-1-phosphate-in-patients-with-osteoarthritis
#18
Esra Aycan Ustyol, Fatih Karaarslan, Seldag Bekpinar, Kagan Ozkuk, Nergis Erdogan
Context • Balneotherapy is one of the most commonly used nonpharmacological interventions for osteoarthritis (OA), but its mechanism of action in relieving pain and stiffness and in improving physical function is not well understood. Studies have found that therapy provokes a series of neuroendocrinal reactions with anti-inflammatory and analgesic effects. Sphingosine-1-phosphate (S1P), a bioactive lipid, has been implicated as an important mediator in the maintenance of physiological processes (eg, vascular barrier integrity) and in pathophysiologic processes such as inflammatory conditions...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646583/sebum-lipids-influence-macrophage-polarization-and-activation
#19
M Lovászi, M Mattii, K Eyerich, Attila Gácsi, Erzsébet Csányi, D Kovács, R Rühl, A Szegedi, L Kemény, M Ståhle, C C Zouboulis, S Eyerich, D Törőcsik
BACKGROUND: As lipids are known to regulate macrophage functions it is reasonable to suppose that a sebocyte - macrophage axis mediated by sebum lipids may exist. OBJECTIVE: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. METHODS: Oil-red-O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets...
June 24, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#20
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
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