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https://www.readbyqxmd.com/read/28727419/next-generation-lipids-in-rna-interference-therapeutics
#1
Stephanie Rietwyk, Dan Peer
RNA is emerging as a potential therapeutic modality for the treatment of incurable diseases. Despite intense research, the advent to clinical utility remains compromised by numerous biological barriers, hence there is a need for sophisticated delivery vehicles. In this aspect, lipid nanoparticles (LNP) are the most advanced platform among non-viral vectors for gene delivery. In this review, we critically review the literature and the reasons for ineffective delivery beyond the liver. We discuss the toxicity issues associated with permanently charged cationic lipids, and then turn our attention to next-generation ionizable cationic lipids...
July 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28727190/tuning-the-effects-of-bacterial-membrane-permeability-through-photo-isomerization-of-antimicrobial-cationic-amphiphiles
#2
Micha Fridman, Joana Salta, Raphael I Benhamou, Ido M Herzog
Several last resort classes of antimicrobial drugs act by permeabilizing cell membranes. Here we demonstrate that insertion of a photo-isomerizable lipid into antimicrobial cationic amphiphiles can modify the intensity of their membrane-permeabilizing activity not only by their concentration but also through light-irradiation. We characterized the photo-isomerization effects of two types of cationic amphiphiles on their bacterial membrane permeabilizing activity and showed that while one photo-isomer inhibited cell growth and division, the other photo-isomer led to a rapid and lethal bacterial membrane-disrupting effect...
July 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28726909/lysine-based-amino-functionalized-lipids-for-gene-transfection-the-protonation-state-in-monolayers-at-the-air-liquid-interface
#3
Stephanie Tassler, Christian Wölk, Christopher Janich, Bodo Dobner, Gerald Brezesinski
Cationic lipids are considered as non-viral carriers for genetic material used in gene therapy. They have no carcinogenic potential and cause low immune response compared to existing viral systems. The protonation degree of these cationic lipids is a crucial parameter for the binding behavior of polynucleotides (e.g., DNA). Newly synthesized peptide-mimic lysine-based amino-functionalized lipids have been investigated in 2D models as monolayers at the air-liquid interface. Standard surface pressure - area isotherms have been measured to prove the layer stability...
July 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28726904/vesicle-aggregates-as-a-model-for-primitive-cellular-assemblies
#4
Tereza Pereira de Souza, Guilherme Volpe Bossa, Pasquale Stano, Frank Steiniger, Sylvio May, Pier Luigi Luisi, Alfred Fahr
Primitive cell models help to understand the role that compartmentalization plays in origin of life scenarios. Here we present a combined experimental and modeling approach towards the construction of simple model systems for primitive cellular assemblies. Charged lipid vesicles aggregate in the presence of oppositely charged biopolymers, such as nucleic acids or polypeptides. Based on zeta potential measurements, dynamic light scattering and cryo-transmission electron-microscopy, we have characterized the behavior of empty and ferritin-filled large unilamellar POPC vesicles, doped with different amounts of cationic (DDAB, CTAB) and anionic (sodium oleate) surfactants, and their aggregation upon the addition of anionic (tRNA, poly-l-glutamic acid) and cationic (poly-l-arginine) biopolymers, respectively...
July 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28725673/efficiency-data-of-intracellular-recombinant-protein-delivery-using-cationic-lipid-coated-silk-fibroin-particle
#5
Woo-Jin Kim, Bong-Soo Kim, Young-Dan Cho, Won-Joon Yoon, Jeong-Hwa Baek, Kyung-Mi Woo, Hyun-Mo Ryoo
This article presents data related to the research article "Fibroin particle-supported cationic lipid layers for highly efficient intracellular protein delivery" and focuses on the delivery efficiency aspects of the fibroin particle-cationic lipid complex (Fibroplex), including its fabrication and the intracellular delivery to the mouse skin tissue. We introduced a stable lipid-particle complex called "Fibroplex", formed by loading cargo protein onto a silk fibroin spherical particle core complexed with cationic liposomes to address the intracellular recombinant protein delivery...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28724897/x-ray-crystallographic-structure-of-a-bacterial-polysialyltransferase-provides-insight-into-the-biosynthesis-of-capsular-polysialic-acid
#6
Christian Lizak, Liam J Worrall, Lars Baumann, Moritz M Pfleiderer, Gesa Volkers, Tianjun Sun, Lyann Sim, Warren Wakarchuk, Stephen G Withers, Natalie C J Strynadka
Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbial peptides and bactericidal antibody production. The biosynthesis of bacterial polySia is catalysed by a single polysialyltransferase (PST) transferring sialic acid from a nucleotide-activated donor to a lipid-linked acceptor oligosaccharide...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722420/salt-promotes-protonation-of-amine-groups-at-air-water-interface
#7
Woongmo Sung, Zaure Avazbaeva, Doseok Kim
Interfacial water reorientation caused by charged Langmuir monolayers consisting of primary fatty amine (ODA) and cationic lipid having quaternary amine headgroup (DPTAP) were investigated by interface-selective vibrational sum-frequency generation spectroscopy. For DPTAP monolayer, initially large sum-frequency intensity from interfacial water OH band decreased steadily by increasing monovalent salt (NaCl, NaI) concentration due to counterion adsorption. On the other hand, ODA/water exhibited significantly smaller sum-frequency intensity than DPTAP/water implying only small portion of protonated amine group (-NH3+) initially existed...
July 19, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28721420/adsorption-of-galloyl-catechin-aggregates-significantly-modulates-membrane-mechanics-in-the-absence-of-biochemical-cues
#8
Takahisa Matsuzaki, Hiroaki Ito, Veronika Chevyreva, Ali Makky, Stefan Kaufmann, Kazuki Okano, Naritaka Kobayashi, Masami Suganuma, Seiichiro Nakabayashi, Hiroshi Y Yoshikawa, Motomu Tanaka
Physical interactions of four major green tea catechin derivatives with cell membrane models were systemically investigated. Catechins with the galloyl moiety caused the aggregation of small unilamellar vesicles and an increase in the surface pressure of lipid monolayers, while those without did not. Differential scanning calorimetry revealed that, in a low concentration regime (≤10 μM), catechin molecules are not significantly incorporated into the hydrophobic core of lipid membranes as substitutional impurities...
July 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28720376/the-increase-in-positively-charged-residues-in-cecropin-d-like-galleria-mellonella-favors-its-interaction-with-membrane-models-that-imitate-bacterial-membranes
#9
José Oñate-Garzón, Alessio Ausili, Marcela Manrique-Moreno, Alejandro Torrecillas, Francisco J Aranda, Edwin Patiño, Juan C Gomez-Fernández
A comparative study of three synthetic peptides, namely neutral Cecropin D-like G. mellonella (WT) and two cationic peptides derived from its sequence, ΔM1 (+5) and ΔM2 (+9) is reported in this work. The influence of charge on the interactions between peptides and membranes and its effect on phase were studied by calorimetric assays. Differential scanning calorimetry (DSC) showed that ΔM2 peptide showed the strongest effect when the membrane contained phosphatidylcholine (PC) and phosphatidylglycerol (PG), increasing membrane fluidization...
July 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28718823/surface-chemistry-interactions-of-cationorm-with-films-by-human-meibum-and-tear-film-compounds
#10
Georgi As Georgiev, Norihiko Yokoi, Yana Nencheva, Nikola Peev, Philippe Daull
Cationorm(®) (CN) cationic nanoemulsion was demonstrated to enhance tear film (TF) stability in vivo possibly via effects on tear film lipid layer (TFLL). Therefore the interactions of CN with human meibum (MGS) and TFLL in vitro and in vivo deserve special study. MGS and CN were spread at the air/water interface of a Langmuir surface balance to ensure a range of MGS/CN oil phase ratios: 20/1, 10/1, 5/1, 3/1, 2/1 and 1/1. The films capability to reorganize during dynamic area changes was evaluated via the surface pressure-area compression isotherms and step/relaxation dilatational rheology studies...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717350/properties-of-native-high-density-lipoproteins-inspire-synthesis-of-actively-targeted-in-vivo-sirna-delivery-vehicles
#11
Kaylin M McMahon, Michael P Plebanek, C Shad Thaxton
Efficient systemic administration of therapeutic short interfering RNA (siRNA) is challenging. High-density lipoproteins (HDL) are natural in vivo RNA delivery vehicles. Specifically, native HDLs: 1) Load single-stranded RNA; 2) Are anionic, which requires charge reconciliation between the RNA and HDL, and 3) Actively target scavenger receptor type B-1 (SR-B1) to deliver RNA. Emphasizing these particular parameters, we employed templated lipoprotein particles (TLP), mimics of spherical HDLs, and self-assembled them with single-stranded complements of, presumably, any highly unmodified siRNA duplex pair after formulation with a cationic lipid...
November 15, 2016: Advanced Functional Materials
https://www.readbyqxmd.com/read/28715002/cationic-folate-mediated-liposomal-delivery-of-bis-arylidene-oxindole-induces-efficient-melanoma-tumor-regression
#12
Chandra Kumar Elechalawar, Kathyayani Sridharan, Abhishek Pal, Mohammed Tanveer Ahmed, Mohammed Yousuf, Susanta Sekhar Adhikari, Rajkumar Banerjee
The folate receptor (FR) is a well-validated and common target for cancer due to its high over-expression in many different cancer cells. Herein, we developed a new FR-targeting ligand (FA8) by conjugating folic acid and a cationic lipid. Owing to its favorable structural property FA8 as a ligand could be accommodated at an unusually higher molar ratio for a ligand-targeted liposome. We then encapsulated a drug-like molecule, bis-arylidene oxindole (NME2), in the targeted liposome. The resulting formulation induced potent caspase-8 up-regulation even in FR-moderately expressing melanoma cells...
July 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28710073/zinc-mediates-the-srebp-scd-axis-to-regulate-lipid-metabolism-in-caenorhabditis-elegans
#13
Jing-Jing Zhang, Jun-Jun Hao, Yu-Ru Zhang, Yan-Li Wang, Ming-Yi Li, Hui-Lai Miao, Xiao-Ju Zou, Bin Liang
Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBPs transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still less understood. Here, we show that reduction of SBP-1, the only homologue of SREBPs in C. elegans, surprisingly leads to high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restores the fat accumulation and fatty acid profile of sbp-1(ep79) mutant...
July 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28709976/glutathione-peroxidase-4-catalyzed-reduction-of-lipid-hydroperoxides-in-membranes-the-polar-head-of-membrane-phospholipids-binds-the-enzyme-and-addresses-the-fatty-acid-hydroperoxide-group-toward-the-redox-center
#14
Giorgio Cozza, Monica Rossetto, Valentina Bosello-Travain, Matilde Maiorino, Antonella Roveri, Stefano Toppo, Mattia Zaccarin, Lucio Zennaro, Fulvio Ursini
GPx4 is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids. This reaction inhibits lipid peroxidation and accounts for enzyme's vital role. Here we investigated the interaction of GPx4 with membrane phospholipids. A cationic surface near the GPx4 catalytic center interacts with phospholipid polar heads. Accordingly, SPR analysis indicates cardiolipin as the phospholipid with maximal affinity to GPx4. Consistent with the electrostatic nature of the interaction, KCl increases the KD...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28704679/ph-sensitive-polymer-modified-liposome-based-immunity-inducing-system-effects-of-inclusion-of-cationic-lipid-and-cpg-dna
#15
Yuta Yoshizaki, Eiji Yuba, Naoki Sakaguchi, Kazunori Koiwai, Atsushi Harada, Kenji Kono
Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects...
July 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28702543/accelerated-molecular-dynamics-simulation-analysis-of-msi-594-in-a-lipid-bilayer
#16
Shruti Mukherjee, Rajiv K Kar, Ravi Prakash Reddy Nanga, Kamal H Mroue, Ayyalusamy Ramamoorthy, Anirban Bhunia
Multidrug resistance against the existing antibiotics is one of the most challenging threats across the globe. Antimicrobial peptides (AMPs), in this regard, are considered to be one of the effective alternatives that can overcome bacterial resistance. MSI-594, a 24-residue linear alpha-helical cationic AMP, has been shown to function via the carpet mechanism to disrupt bacterial membrane systems. To better understand the role of lipid composition in the function of MSI-594, in the present study, eight different model membrane systems have been studied using accelerated molecular dynamics (aMD) simulations...
July 13, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28702427/antioxidant-and-anticholinesterase-potential-of-two-nigerian-bitter-yams-using-a-simulated-gastrointestinal-digestion-model-and-conventional-extraction
#17
Sule Ola Salawu, Praise Blessing Ajiboye, Akintunde Afolabi Akindahunsi, Aline Augusti Boligon
The purpose of this study was to evaluate the antioxidant and anticholinesterase activities of yellow and white bitter yams from South Western Nigeria using methanolic extraction and simulated gastrointestinal digestion models. The phenolic compounds in the bitter yam varieties were evaluated by high performance liquid chromatography with a diode array detector (HPLC-DAD). The total phenolic content of the bitter yams was measured by the Folin-Ciocalteu method, reductive potential by assessing the ability of the bitter yam to reduce FeCl3 solution, and the antioxidant activities were determined by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(·)) scavenging activity, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(·+)) scavenging activity, nitric oxide radical (NO(·)) scavenging ability, hydroxyl radical scavenging ability, and ability to inhibit Fe(2+)-induced lipid oxidation...
June 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28701285/association-of-divalent-cations-and-insulin-resistance-with-thyroid-hormones-in-patients-with-type-2-diabetes-mellitus
#18
Rajendran Jayanthi, Abu Raghavan Srinivasan, Niranjan Gopal, Ramesh Ramaswamy
AIM: The study was primarily aimed at investigating the association of Magnesium and Zinc levels in the serum of adult Non- obese and Obese type 2 diabetic patients, with particular reference to thyroid comorbidity. METHODS: 108 patients with T2DM of both genders (24 Non obese and 84 Obese) were enrolled from a tertiary health care unit in Puducherry. The cardio-metabolic risk factors were assessed through body mass index, Waist hip ratio, blood pressure, fasting blood glucose, lipid profile and glycated haemoglobin...
July 3, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28700927/charged-antimicrobial-peptides-can-translocate-across-membranes-without-forming-channel-like-pores
#19
Jakob P Ulmschneider
How can highly charged, cationic antimicrobial peptides (AMPs) translocate across hydrophobic lipid bilayers despite the prohibitive energetic penalty to do so? A common explanation has been the formation of peptide-lined channels. However, for most AMPs, no structures of membrane pores have been found despite clear evidence of membrane leakage and antimicrobial activity. The study here suggests an alternative and simple reason: for the AMP PGLa from Xenopus laevis (charge +5), such pores are not needed to explain both leakage and peptide translocation...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28695852/the-multidrug-resistance-transporter-mdfa-from-escherichia-coli-crystallization-and-x-ray-diffraction-analysis
#20
Kumar Nagarathinam, Frank Jaenecke, Yoshiko Nakada-Nakura, Yunhon Hotta, Kehong Liu, So Iwata, Milton T Stubbs, Norimichi Nomura, Mikio Tanabe
The active efflux of antibiotics by multidrug-resistance (MDR) transporters is a major pathway of drug resistance and complicates the clinical treatment of bacterial infections. MdfA is a member of the major facilitator superfamily (MFS) from Escherichia coli and provides resistance to a wide variety of dissimilar toxic compounds, including neutral, cationic and zwitterionic substances. The 12-transmembrane-helix MdfA was expressed as a GFP-octahistidine fusion protein with a TEV protease cleavage site. Following tag removal, MdfA was purified using two chromatographic steps, complexed with a Fab fragment and further purified using size-exclusion chromatography...
July 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
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