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https://www.readbyqxmd.com/read/29452131/synergism-between-a-cell-penetrating-peptide-and-a-ph-sensitive-cationic-lipid-in-efficient-gene-delivery-based-on-double-coated-nanoparticles
#1
Ikramy A Khalil, Seigo Kimura, Yusuke Sato, Hideyoshi Harashima
We report on the development of a highly efficient gene delivery system based on synergism between octaarginine (R8), a representative cell penetrating peptide, and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high density of R8 on the surface of YSK05 nanoparticles (NPs) that contained encapsulated plasmid DNA resulted in the formation of positively charged NPs with improved transfection efficiency. To avoid the development of a net positive charge, we controlled the density and topology of the R8 peptide through the use of a two-step coating methodology, in which the inner lipid coat was modified with a low density of R8 which was then covered with an outer neutral YSK05 lipid layer...
February 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29449809/digging-into-lipid-membrane-permeation-for-cardiac-ion-channel-blocker-d-sotalol-with-all-atom-simulations
#2
Kevin R DeMarco, Slava Bekker, Colleen E Clancy, Sergei Y Noskov, Igor Vorobyov
Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29448216/development-of-an-indolicidin-derived-peptide-by-reducing-membrane-perturbation-to-decrease-cytotoxicity-and-maintain-gene-delivery-ability
#3
Ching-Wei Tsai, Ze-Wei Lin, Wen-Fang Chang, Yi-Fan Chen, Wei-Wen Hu
Indolicidin (IL) is a cationic antimicrobial peptide and our previous study has demonstrated its potential as a cell penetrating peptide (CPP) to promote gene delivery. However, the cytotoxicity of IL arisen from its membrane perturbation capacity may restrict its clinical application. To promote gene delivery safety and efficiency, an almost mirror-symmetric IL derivative, SAP10 (RRWKFFPWRR-CONH 2 ), was designed in this study. All-atom molecular dynamics (MD) simulations were performed to understand the association between SAP10 and model lipid bilayers...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29441956/curcumin-loaded-cationic-solid-lipid-nanoparticles-as-a-potential-platform-for-the-treatment-of-skin-disorders
#4
M L Gonçalez, R B Rigon, M A Pereira-da-Silva, M Chorilli
Curcumin (CUM) possesses therapeutic activity against diverse skin disorders (SD); however, its clinical use faces many challenges related to physicochemical and bioavailability characteristics, that can be solve designing a new drug delivery system for CUM to treat SD. Cationic solid lipid nanoparticles (CSLN) were developed and physicochemically analyzed. The ingredients and methods adopted in this study promoted the successful preparation of CSLN with a monodispersed particle size of 218.4-238.6 nm and a polydispersity index of 0...
December 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29440705/innovative-lipid-based-carriers-containing-cationic-derivatives-of-polyisoprenoid-alcohols-augment-the-antihypertensive-effectiveness-of-candesartan-in-spontaneously-hypertensive-rats
#5
Olga Gawryś, Iwona Baranowska, Katarzyna Gawarecka, Ewa Świeżewska, Jolanta Dyniewicz, Krzysztof H Olszyński, Marek Masnyk, Marek Chmielewski, Elżbieta Kompanowska-Jezierska
Novel lipid-based carriers, composed of cationic derivatives of polyisoprenoid alcohols (amino-prenols, APrens) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), were designed. The carriers, which were previously shown to be nontoxic to living organisms, were now tested if suitable for administration of candesartan, an antihypertensive drug. Spontaneously hypertensive rats (SHR) received injections of candesartan (0.1 mg/kg body weight per day; s.c.) in freshly prepared carriers for two weeks. The rats' arterial pressure was measured by telemetry...
February 13, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29428024/effect-of-systemic-triphenylphosphonium-on-organ-function-and-oxidative-stress
#6
Rebecca D Powell, Donna A Goodenow, A Britton Christmas, Iain H Mckillop, Susan L Evans
Conditions of systemic stress can lead to increased reactive oxygen species production, mitochondrial dysfunction, systemic inflammation, and multiorgan dysfunction. Triphenylphosphonium (TPP+) is a lipophilic cation used to target therapeutics to mitochondria. We sought to determine the effects of TPP+ on mitochondrial integrity. Male rats were anesthetized and TPP+ (5 mg/kg) or vehicle (saline) was administered intravenously 30-minutes after anesthesia initiation and intraperitoneally (20 mg/kg) 60-minutes later...
January 1, 2018: American Surgeon
https://www.readbyqxmd.com/read/29425725/thermal-actuation-in-trpv1-role-of-embedded-lipids-and-intracellular-domains
#7
Corey Melnick, Massoud Kaviany
The transient response potential cation channel TRPV1 responds to high temperature, but many of the mechanisms driving its thermal actuation remain unclear. Its recently resolved structure has enabled a number of molecular dynamics (MD) studies focused on illuminating these mechanisms. We add to these efforts by performing the first all-atom MD simulations of its most recently resolved structure at different temperatures. While the complete, thermally induced transition of TRPV1 from its closed to open configuration remains elusive, our analysis of the hydrogen bonding networks, thermodynamics, hydration, and principal components of motion provide a wealth of information on the mechanisms which initiate or influence the thermal opening in TRPV1...
February 6, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29422286/visit-to-visit-lipid-variability-clinical-significance-effects-of-lipid-lowering-treatment-and-pharmaco-genetics
#8
REVIEW
Roelof A J Smit, Johan Wouter Jukema, Iris Postmus, Ian Ford, Pieternella Eline Slagboom, Bastiaan T Heijmans, Saskia Le Cessie, Stella Trompet
In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial...
January 11, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29419285/increased-degree-of-unsaturation-in-the-lipid-of-antifungal-cationic-amphiphiles-facilitates-selective-fungal-cell-disruption
#9
Kfir B Steinbuch, Raphael I Benhamou, Lotan Levin, Reuven Stein, Micha Fridman
Antimicrobial cationic amphiphiles derived from aminoglycosides act through cell membrane permeabilization but have limited selectivity for microbial cell membranes. Herein, we report that an increased degree of unsaturation in the fatty acid segment of antifungal cationic amphiphiles derived from the aminoglycoside tobramycin significantly reduced toxicity to mammalian cells. A collection of tobramycin-derived cationic amphiphiles substituted with C18 lipid chains varying in degree of unsaturation and double bond configuration were synthesized...
February 8, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29413614/antifungal-activity-of-newly-synthesized-chemodegradable-dicephalic-type-cationic-surfactants
#10
E Paluch, A Piecuch, E Obłąk, Ł Lamch, K A Wilk
The studies were aimed to contribute to the elucidation of the relationships between structure of the double-headed cationic surfactants - N,N-bis[3,3'-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3'-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31), which are of particular interest, as they contain a labile amide group in the molecule and their antifungal activity. Therefore, the minimal inhibitory and fungicidal concentrations (MIC and MFC) of dicephalic surfactants against various fungi were tested using standardized methods...
January 31, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29412464/effects-of-bentonite-bgp35b-p-on-the-gut-microbiota-of-mice-fed-a-high-fat-diet
#11
Eun-Sook Lee, Eun-Ji Song, So-Young Lee, So-Lim Park, Daeyoung Kim, Daniel Kim, Jae-Hwan Kim, Seong-Il Lim, Young-Do Nam
BACKGROUND: Bentonite is a natural clay mineral with health-promoting effects due to high adsorption abilities with high cation exchange capacity. Previously, we found an anti-obesity effect for the Bgp35b-p bentonite produced in South Korea where its high adsorbent ability of dietary lipids possibly partially removed lipidic environment in the gut (under revision). It hypothesized that Bgp35b-p affects the intestinal microbial community, thus the microbial changes were investigated via the next generation sequencing targeting bacterial 16s rRNA gene and the bioinformatics using QIIME were performed in feces of C57BL/6 male mice fed a HFD with the Bgp35b-p...
February 7, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29412454/antioxidant-properties-of-astaxanthin-in-oil-in-water-emulsions-with-differently-charged-emulsifiers-under-chlorophyll-photosensitization
#12
BoRa Yi, Mi-Ja Kim, JaeHwan Lee
The antioxidative or prooxidative properties of astaxanthin at the concentrations of 0, 10, and 100 μM were determined in oil-in-water (O/W) emulsions containing neutral, anionic, and cationic emulsifiers, which was Tween 20, sodium dodecyl sulfate, cetyltrimethylammonium bromide (CTAB), respectively, under chlorophyll photosensitization. The oxidative parameters and headspace volatiles were analyzed in O/W emulsions. In the 24 h period of visible light irradiation, 100 μM of astaxanthin acted as an antioxidant in O/W emulsions containing neutral and anionic emulsifiers...
February 7, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29412195/in-situ-examination-of-a-charged-amino-acid-induced-structural-change-in-lipid-bilayers-by-sum-frequency-generation-vibrational-spectroscopy
#13
Jiahui Zhang, Weilai Yang, Junjun Tan, Shuji Ye
The interactions between amino acids (AAs) and membranes represent various short-range and long-range interactions for biological phenomena; however, they are still poorly understood. In this study, we used cationic lysine and arginine as AA models, and systematically investigated the interactions between charged AAs and lipid bilayers using sum frequency generation vibrational spectroscopy (SFG-VS) in situ and in real time. The AA-induced dynamic structural changes of the lipid bilayer were experimentally monitored using the spectral features of CD2, CD3, the lipid head phosphate, and carbonyl groups in real time...
February 7, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29406731/interaction-of-tyrosine-analogues-with-quaternary-ammonium-head-groups-at-micelle-water-interface-and-contrasting-effect-of-molecular-folding-on-hydrophobic-outcome-and-end-cap-geometry
#14
Gulmi Chakraborty, Madhurima Paul Chowdhury, Puthusserickal Abdulrahiman Hassan, Koji Tsuchiya, Kanjiro Torigoe, Swapan K Saha
The surface property of the cationic micelles of cetyltrimethylammonium bromide (CTAB) in aqueous medium is highly modified in presence of tyrosineoctyl ester (TYOE) and tyrosinedodecyl ester (TYDE), the models for aromatic aminoacid side chains of transmembrane proteins. While the synergistic interaction between quaternary ammonium head group of CTAB and the π-electron cloud of aromatic aminoacid ester is influenced by the relative orientation vis-à-vis unusual molecular geometry of the later, this eventually triggers morphology transition of the spherical micelle to cylindrical/wormlike micelles and impart strong viscoelasticity in the medium...
February 6, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29405165/the-expression-of-the-new-epididymal-luminal-protein-of-pdz-domain-containing-1-is-decreased-in-asthenozoospermia
#15
A-Juan Liang, Gui-Shuan Wang, Ping Ping, Shuang-Gang Hu, Yu Lin, Yi Ma, Zheng-Zheng Duan, Han-Shu Wang, Fei Sun
Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ)...
January 19, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29401708/role-of-cationic-side-chains-in-the-antimicrobial-activity-of-c18g
#16
Eric M Kohn, David J Shirley, Lubov Arotsky, Angela M Picciano, Zachary Ridgway, Michael W Urban, Benjamin R Carone, Gregory A Caputo
Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. The peptide C18G has been shown to be a selective, broad spectrum AMP with a net +8 cationic charge from seven lysine residues in the sequence. In this work, the cationic Lys residues were replaced with other natural or non-proteinogenic cationic amino acids: arginine, histidine, ornithine, or diaminopropionic acid...
February 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29401434/melittin-induced-permeabilization-re-sealing-and-re-permeabilization-of-e-%C3%A2-coli-membranes
#17
Zhilin Yang, Heejun Choi, James C Weisshaar
The permeabilization of model lipid bilayers by cationic peptides has been studied extensively over decades, with the bee-sting toxin melittin perhaps serving as the canonical example. However, the relevance of these studies to the permeabilization of real bacterial membranes by antimicrobial peptides remains uncertain. Here, we employ single-cell fluorescence microscopy in a detailed study of the interactions of melittin with the outer membrane (OM) and the cytoplasmic membrane (CM) of live Escherichia coli...
January 23, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29393934/the-interfacial-electrostatic-potential-modulates-the-insertion-of-cell-penetrating-peptides-into-lipid-bilayers
#18
Matías A Via, Joaquín Klug, Natalia Wilke, Luis S Mayorga, M G Del Pópolo
Cell-penetrating peptides (CPP) are short sequences of cationic amino-acids that show a surprising ability to traverse lipid bilayers. CPP are considered to be some of the most effective vectors to introduce membrane-impermeable cargos into cells, but the molecular basis of the membrane translocation mechanisms and its dependence on relevant membrane physicochemical properties have yet to be fully determined. In this paper we resort to Molecular Dynamics simulations and experiments to investigate how the electrostatic potential across the lipid/water interface affects the insertion of hydrophilic and amphipathic CPP into two-dimensional lipid structures...
February 2, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29382763/phosphatidylinositol-4-5-bisphosphate-regulates-calcium-gating-of-small-conductance-cation-channel-tmem16f
#19
Wenlei Ye, Tina W Han, Layla M Nassar, Mario Zubia, Yuh Nung Jan, Lily Yeh Jan
TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca2+-activated current, we found that the TMEM16F Ca2+-response is desensitized by a brief exposure to high intracellular Ca2+, which is associated with depletion of phosphatidylinositol-(4, 5)-bisphosphate (PIP2) from the inner leaflet of the membrane...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29377649/development-of-ph-sensitive-cationic-pegylated-solid-lipid-nanoparticles-for-selective-cancer-targeted-therapy
#20
Chih-Hung Chuang, Pao-Chu Wu, Teng-Huang Tsai, Yi-Ping Fang, Yi-Hung Tsai, Ta-Chun Cheng, Chien-Chaio Huang, Ming-Yii Huang, Fang-Ming Chen, Yuan-Chin Hsieh, Wen-Wei Lin, Ming-Jun Tsai, Tian-Lu Cheng
Solid lipid nanoparticles (SLNs) are suitable candidates for the delivery of various anti-cancer drugs. However, currently insufficient tumor-permeability and non-specific uptake by the reticuloendothelial system limits the application of SLNs. Here, we developed novel pH-sensitive cationic polyoxyethylene (PEGylated) SLNs (PEG-SLNs+) that could accumulate long-term at various tumor sites to enhance the therapeutic efficiency of camptothecin (CPT). These CPT-loaded PEG-SLNs+ (CPT-PEG-SLNs+) were spherical nanoparticles, with small size (∼52...
February 2017: Journal of Biomedical Nanotechnology
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