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https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#1
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29281244/high-density-lipoprotein-nanobiologics-for-precision-medicine
#2
Willem J M Mulder, Mandy M T van Leent, Marnix Lameijer, Edward A Fisher, Zahi A Fayad, Carlos Pérez-Medina
Nature is an inspirational source for biomedical engineering developments. Particularly, numerous nanotechnological approaches have been derived from biological concepts. For example, among many different biological nanosized materials, viruses have been extensively studied and utilized, while exosome research has gained much traction in the 21st century. In our body, fat is transported by lipoproteins, intriguing supramolecular nanostructures that have important roles in cell function, lipid metabolism, and disease...
December 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29274774/nanotherapy-for-alzheimer-s-disease-and-vascular-dementia-targeting-senile-endothelium
#3
REVIEW
Joseph S D'Arrigo
Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted "lipid-coated microbubble" [LCM]/"nanoparticle-derived" [ND] (or LCM/ND) nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine...
December 8, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/29226138/effects-of-astaxanthin-on-reverse-cholesterol-transport-and-atherosclerosis-in-mice
#4
Tang-Bin Zou, Shan-Shan Zhu, Fei Luo, Wei-Qiao Li, Xue-Rong Sun, Hong-Fu Wu
High plasma level of HDL-cholesterol (HDL-C) has been consistently associated with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an antiatherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the possibility of further reducing the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective activity of HDL, which has been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) and then transport it back to the liver for excretion into bile and eventually into the feces...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29199275/lysosomal-integral-membrane-protein-2-as-a-phospholipid-receptor-revealed-by-biophysical-and-cellular-studies
#5
Karen S Conrad, Ting-Wen Cheng, Daniel Ysselstein, Saskia Heybrock, Lise R Hoth, Boris A Chrunyk, Christopher W Am Ende, Dimitri Krainc, Michael Schwake, Paul Saftig, Shenping Liu, Xiayang Qiu, Michael D Ehlers
Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) contributes to endosomal and lysosomal function. LIMP-2 deficiency is associated with neurological abnormalities and kidney failure and, as an acid glucocerebrosidase receptor, impacts Gaucher and Parkinson's diseases. Here we report a crystal structure of a LIMP-2 luminal domain dimer with bound cholesterol and phosphatidylcholine. Binding of these lipids alters LIMP-2 from functioning as a glucocerebrosidase-binding monomer toward a dimeric state that preferentially binds anionic phosphatidylserine over neutral phosphatidylcholine...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163190/sr-bi-mediated-transcytosis-of-hdl-in-brain-microvascular-endothelial-cells-is-independent-of-caveolin-clathrin-and-pdzk1
#6
Karen Y Fung, Changsen Wang, Steffen Nyegaard, Bryan Heit, Gregory D Fairn, Warren L Lee
The vascular endothelium supplying the brain exhibits very low paracellular and transcellular permeability and is a major constituent of the blood-brain barrier. High-density lipoprotein (HDL) crosses the blood-brain barrier by transcytosis, but technical limitations have made it difficult to elucidate its regulation. Using a combination of spinning-disc confocal and total internal reflection fluorescence microscopy, we examined the uptake and transcytosis of HDL by human primary brain microvascular endothelial cell monolayers...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29162870/hdl-particles-incorporate-into-lipid-bilayers-a-combined-afm-and-single-molecule-fluorescence-microscopy-study
#7
Birgit Plochberger, Clemens Röhrl, Johannes Preiner, Christian Rankl, Mario Brameshuber, Josef Madl, Robert Bittman, Robert Ros, Erdinc Sezgin, Christian Eggeling, Peter Hinterdorfer, Herbert Stangl, Gerhard J Schütz
The process, how lipids are removed from the circulation and transferred from high density lipoprotein (HDL) - a main carrier of cholesterol in the blood stream - to cells, is highly complex. HDL particles are captured from the blood stream by the scavenger receptor, class B, type I (SR-BI), the so-called HDL receptor. The details in subsequent lipid-transfer process, however, have not yet been completely understood. The transfer has been proposed to occur directly at the cell surface across an unstirred water layer, via a hydrophobic channel in the receptor, or after HDL endocytosis...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29155143/obeticholic-acid-raises-ldl-cholesterol-and-reduces-hdl-cholesterol-in-the-diet-induced-nash-din-hamster-model
#8
François Briand, Emmanuel Brousseau, Marjolaine Quinsat, Rémy Burcelin, Thierry Sulpice
The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-induced NASH (DIN) hamster model and evaluated the impact of OCA...
November 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29122594/inhibition-of-the-nlrp3-inflammasome-attenuates-foam-cell-formation-of-thp-1-macrophages-by-suppressing-ox-ldl-uptake-and-promoting-cholesterol-efflux
#9
Liang Chen, Qiying Yao, Siwei Xu, Hongyan Wang, Peng Qu
The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the development of atherosclerosis. The activated NLRP3 inflammasome has been reported to promote macrophage foam cell formation, but not all studies have obtained the same result, and how NLRP3 inflammasome is involved in the formation of foam cells remains elusive. We used selective NLRP3 inflammasome inhibitors and NLRP3-deficient THP-1 cells to assess the effect of NLRP3 inflammasome inhibition on macrophage foam cell formation, oxidized low-density lipoprotein (ox-LDL) uptake, esterification, and cholesterol efflux, as well as the expression of associated proteins...
November 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29092018/the-function-of-hdl-and-ldl-in-the-maintenance-of-mouse-ovarian-steroid-balance
#10
Xin-Lian Chang, Lisheng Liu, Naiqiang Wang, Zi-Jiang Chen, Cong Zhang
The membrane proteins, low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SR-BI, gene name Scarb1), are lipoprotein receptors that play central roles in lipoprotein metabolism. Cholesterol bound in high-density lipoprotein (HDL) and LDL is transported into cells mainly by SR-BI and LDLR. The relative contribution of LDL and HDL to the steroidogenic cholesterol pool varies among species and may vary among tissues within one species. To investigate which of these pathways is more important in the supply of cholesterol in mouse ovary, we utilized immunohistochemistry, western blotting, RNAi and RT-PCR as well as Ldlr-/- mice to explore the uptake of HDL and LDL in the ovary...
October 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29065536/comparison-of-the-micellar-incorporation-and-the-intestinal-cell-uptake-of-cholecalciferol-25-hydroxycholecalciferol-and-1-%C3%AE-hydroxycholecalciferol
#11
Charles Desmarchelier, Marielle Margier, Damien P Prévéraud, Marion Nowicki, Véronique Rosilio, Patrick Borel, Emmanuelle Reboul
In the context of the global prevalence of vitamin D insufficiency, we compared two key determinants of the bioavailability of 3 vitamin D forms with significant biopotencies: cholecalciferol, 25-hydroxycholecalciferol and 1-α-hydroxycholecalciferol. To this aim, we studied their incorporation into synthetic mixed micelles and their uptake by intestinal cells in culture. Our results show that 1-α-hydroxycholecalciferol was significantly more solubilized into mixed micelles compared to the other forms (1.6-fold and 2...
October 23, 2017: Nutrients
https://www.readbyqxmd.com/read/29030613/lipopolysaccharide-enters-the-rat-brain-by-a-lipoprotein-mediated-transport-mechanism-in-physiological-conditions
#12
Alejandra Vargas-Caraveo, Aline Sayd, Sandra R Maus, Javier R Caso, José L M Madrigal, Borja García-Bueno, Juan C Leza
Physiologically, lipopolysaccharide (LPS) is present in the bloodstream and can be bound to several proteins for its transport (i.e.) LPS binding protein (LBP) and plasma lipoproteins). LPS receptors CD14 and TLR-4 are constitutively expressed in the Central Nervous System (CNS). To our knowledge, LPS infiltration in CNS has not been clearly demonstrated. A naturalistic experiment with healthy rats was performed to investigate whether LPS is present with its receptors in brain. Immunofluorescences showed that lipid A and core LPS were present in circumventricular organs, choroid plexus, meningeal cells, astrocytes, tanycytes and endothelial cells...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28984832/the-role-of-omega-3-fatty-acids-in-reverse-cholesterol-transport-a-review
#13
REVIEW
Alex Pizzini, Lukas Lunger, Egon Demetz, Richard Hilbe, Guenter Weiss, Christoph Ebenbichler, Ivan Tancevski
The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8...
October 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28974560/malignant-phenotypes-in-metastatic-melanoma-are-governed-by-sr-bi-and-its-association-with-glycosylation-and-stat5-activation
#14
Katharina Kinslechner, David Schörghofer, Birgit Schütz, Maria Vallianou, Bettina Wingelhofer, Wolfgang Mikulits, Clemens Röhrl, Markus Hengstschläger, Richard Moriggl, Herbert Stangl, Mario Mikula
Metastatic melanoma is hallmarked by elevated glycolytic flux and alterations in cholesterol homeostasis. The contribution of cholesterol transporting receptors for the maintenance of a migratory and invasive phenotype is not well defined. Here, the scavenger receptor class B type I (SCARB1/SR-BI), a high-density lipoprotein (HDL) receptor, was identified as an estimator of melanoma progression in patients. We further aimed to identify the SR-BI controlled gene expression signature and its related cellular phenotypes...
October 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28941732/the-adaptor-protein-alpha-syntrophin-is-reduced-in-human-non-alcoholic-steatohepatitis-but-is-unchanged-in-hepatocellular-carcinoma
#15
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Thomas S Weiss, Christa Buechler
The adaptor protein alpha-syntrophin (SNTA) is differentially expressed in varying types of cancer and affects triglyceride levels, inflammatory response and cell proliferation. However, little is known about the expression of SNTA in liver diseases. Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation and eventually fibrosis, and may progress to hepatocellular carcinoma (HCC). Here, SNTA mRNA was analyzed in liver tissues from 71 non-alcoholic fatty liver disease patients and 32 controls to assess associations with disease characteristics...
September 21, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28910310/gugulipid-causes-hypercholesterolemia-leading-to-endothelial-dysfunction-increased-atherosclerosis-and-premature-death-by-ischemic-heart-disease-in-male-mice
#16
Andrea Leiva, Susana Contreras-Duarte, Ludwig Amigo, Esteban Sepúlveda, Mauricio Boric, Verónica Quiñones, Dolores Busso, Attilio Rigotti
For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI), a high-density lipoprotein (HDL) receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28863273/2-3-4-5-tetrahydroxystilbene-2-o-%C3%AE-d-glycoside-attenuates-atherosclerosis-in-apolipoprotein%C3%A2-e-deficient-mice-role-of-reverse-cholesterol-transport
#17
Xuemeng Chen, Kun Tang, Yi Peng, XiaoLe Xu
The aim of this study was to evaluate the potential effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE(-/-) mice, and explore the mechanisms involved. Our data showed that after 8 weeks of treatment, TSG ameliorated serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and increased serum levels of high density lipoprotein cholesterol in ApoE(-/-) mice. TSG suppressed hepatic steatosis, the formation of atherosclerotic lesions, and the formation of macrophage foam cells in ApoE(-/-) mice...
September 1, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28830907/plasma-cholesterol-homeostasis-hdl-remodeling-and-function-during-the-acute-phase-reaction
#18
Francesca Zimetti, Stefano De Vuono, Monica Gomaraschi, Maria Pia Adorni, Elda Favari, Nicoletta Ronda, Maria Anastasia Ricci, Fabrizio Veglia, Laura Calabresi, Graziana Lupattelli
Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition, and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes, or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44...
October 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28830501/high-density-lipoproteins-suppress-a%C3%AE-induced-pbmc-adhesion-to-human-endothelial-cells-in-bioengineered-vessels-and-in-monoculture
#19
Jérôme Robert, Emily B Button, Sophie Stukas, Guilaine K Boyce, Ebrima Gibbs, Catherine M Cowan, Megan Gilmour, Wai Hang Cheng, Sonja K Soo, Brian Yuen, Arvin Bahrabadi, Kevin Kang, Iva Kulic, Gordon Francis, Neil Cashman, Cheryl L Wellington
BACKGROUND: Alzheimer's Disease (AD), characterized by accumulation of beta-amyloid (Aβ) plaques in the brain, can be caused by age-related failures to clear Aβ from the brain through pathways that involve the cerebrovasculature. Vascular risk factors are known to increase AD risk, but less is known about potential protective factors. We hypothesize that high-density lipoproteins (HDL) may protect against AD, as HDL have vasoprotective properties that are well described for peripheral vessels...
August 22, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28828863/rerouting-native-hdl-to-predetermined-receptors-for-improved-tumor-targeted-gene-silencing-therapy
#20
Yang Ding, Yue Han, Ruoning Wang, Yazhe Wang, Cheng Chi, Ziqiang Zhao, Huaqing Zhang, Wei Wang, Lifang Yin, Jianping Zhou
High-density lipoprotein (HDL) is an outstanding biocompatible nanovector for tumor-targeted delivery of multimodel drugs in cancer therapy. However, this seemingly promising delivery platform demonstrates an adverse accumulation in liver and adrenal due to the primary expression of natural target scavenger receptor class B type I (SR-BI), which overexpressed in malignant cells as well. Therefore, we endowed native HDLs with rerouting capacity, that is, enabling HDLs to get away from natural receptors (SR-BI) to selectively alternate tumor-rich receptors...
September 13, 2017: ACS Applied Materials & Interfaces
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