Liposomes with cerasome-forming lipids as gene therapy vectors

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Electrostatic Interactions ◽  
Membrane Surface ◽  
Immunological Response ◽  
Basic Research ◽  
Systemic Circulation ◽  
Cationic Lipids ◽  
Transport Systems ◽  
Component Selection ◽  
Polar Groups ◽  
Gene Therapy Vectors

Basic research focuses on liposome transport systems as non-viral ways of transferring genetic and therapeutic substances. Due to electrostatic interactions between positive polar groups of cationic lipids and the negatively charged cell membrane surface, nucleic acids may readily be transported into cells as part of lipoplexes. Cationic liposomes, however, have a number of well-known problems, including low stability, toxicity, and a potential for severe immunological response. Recent research has revealed, however, that by increasing the system with additional components such as cerasome-forming lipids, these problems may be solved. They aid in the prolongation of the release of a beneficial liposome load in cells by increasing vesicle stability in the systemic circulation. This circumstance broadens the applications for liposomal systems. As a consequence, using varied lipids can create numerous liposomes for use in a range of medical fields. Nonviral delivery approaches based on hybrid liposomes with suitable structural component selection may be a possible response to a number of medical concerns, and further study is urgently needed.

Measurement of trace metal influx in plants: a case study with Co

2004 ◽  
Vol 31 (9) ◽  
pp. 941 ◽  
Author(s):  
Rob Reid ◽  
Juhong Liu
Keyword(s):  
Trace Metals ◽  
Trace Metal ◽  
Membrane Surface ◽  
Transport Systems ◽  
Ph Effects ◽  
Flux Measurements ◽  
Membrane Surface Charge ◽  
Broad Specificity

The analysis of transport systems involved in the uptake of trace metals in plants is complicated by technical difficulties associated with measurement of uptake and by the likely presence of multiple transporters with broad specificity. In this study, influx of Co was used to illustrate the problems involved and potential solutions. Issues surrounding kinetic descriptions of transport, multiple uptake systems, specificity of transporters, pH effects and the role of membrane surface charge in determining fluxes are addressed. A list of criteria for validation of flux measurements is provided.

scholarly journals Hypoxic-Ischaemic Encephalopathy and the Blood-Brain Barrier in Neonates

2017 ◽  
Vol 39 (1-4) ◽  
pp. 49-58 ◽  
Author(s):  
Wei Ling Amelia Lee ◽  
Adina T. Michael-Titus ◽  
Divyen K. Shah
Keyword(s):  
Blood Brain Barrier ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Cerebral Injury ◽  
Brain Barrier ◽  
Transport Systems ◽  
Permeability Barrier ◽  
Cell Based Therapy ◽  
Blood Brain ◽  
The Brain

This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level. The BBB is a permeability barrier which separates a large majority of brain areas from the systemic circulation. The concept of a physiological BBB is based at the anatomical level on the neurovascular unit (NVU). The NVU consists of various cellular components that jointly regulate the exchanges that occur at the interface between the systemic circulation and the brain parenchyma. There is increased understanding of the contribution of the components of the NVU, e.g., astrocytes and pericytes, to the maintenance of this physiological barrier. We also explore the development of therapeutic options in HIE, such as harnessing the transport systems in the BBB, to enable the delivery of large molecules with molecular Trojan horse technology, and the reinforcement of the physical barrier with cell-based therapy which utilizes endothelial progenitor cells and stem cells.

scholarly journals Lipid anchoring and electrostatic interactions target the phospholipase NOT-LIKE-DAD to pollen endo-plasma membrane

2020 ◽  
Author(s):  
Laurine M. Gilles ◽  
Veronica La Padula ◽  
Nathanaël M.A. Jacquier ◽  
Jean-Pierre Martinant ◽  
Peter M. Rogowsky ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Electrostatic Interactions ◽  
Membrane Surface ◽  
Male Gamete ◽  
Targeted Mutagenesis ◽  
Major Constituent ◽  
Sperm Cells ◽  
Wild Type Female ◽  
Haploid Embryos ◽  
Membrane Surface Charge

AbstractPhospholipases are ubiquitous enzymes that cleave phospholipids, one major constituent of membranes. They are thus essential for many developmental processes, including male gamete development. In flowering plants, mutation of phospholipase NOT-LIKE-DAD (NLD) leads to peculiar defects in sexual reproduction. Indeed, pollination of a wild-type female with mutant pollen generates haploid embryos containing solely maternal genetic information. Contrary to previous reports NLD does not localize to cytosol and plasma membrane (PM) of sperm cells but to the pollen endo-plasma membrane (endo-PM), a specific membrane derived from the PM of the pollen vegetative cell that encircles the two sperm cells. Pharmacological approaches coupled with targeted mutagenesis revealed that lipid anchoring together with electrostatic interactions between membrane and NLD are involved in the attachment of NLD to this atypical endo-PM. Membrane surface-charge and anionic lipid bio-sensors indicated that phosphatidylinositol-4,5-bisphosphate (PIP(4,5)P2) is enriched in the endo-PM as compared to the PM. Our results uncover a unique example of how membrane electrostatic properties can specify a unique polar domain (i.e. endo-PM), which is critical for plant reproduction and gamete formation.

scholarly journals Insights into the Polyhexamethylene Biguanide (PHMB) Mechanism of Action on Bacterial Membrane and DNA: A Molecular Dynamics Study

2020 ◽  
Author(s):  
Shahin Sowlati-Hashjin ◽  
Paola Carbone ◽  
Mikko Karttunen
Keyword(s):  
Molecular Dynamics ◽  
Electrostatic Interactions ◽  
Membrane Surface ◽  
Md Simulations ◽  
Phospholipid Bilayer ◽  
Phospholipid Membrane ◽  
Replication Process ◽  
Polyhexamethylene Biguanide ◽  
Phosphate Backbone ◽  
Pass Through

AbstractPolyhexamethylene biguanide (PHMB) is a cationic polymer with antimicrobial and antiviral properties. It has been commonly accepted that the antimicrobial activity is due the ability of PHMB to perforate the bacterial phospholipid membrane leading ultimately to its death. In this study we show by the means of atomistic molecular dynamics (MD) simulations that while the PHMB molecules attach to the surface of the phospholipid bilayer and partially penetrate it, they do not cause any pore formation at least within the microsecond simulation times. The polymers initially adsorb onto the membrane surface via the favourable electrostatic interactions between the phospholipid headgroups and the biguanide groups, and then partially penetrate the membrane slightly disrupting its structure. This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively ‘bind’ to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways.TOC Graphic

scholarly journals DETERMINATION OF THE DELAY TIME OF THE BUS DEPARTURE FROM THE STOP POINT LOCATED NEAR A REGULATED CROSSROADS

2020 ◽  
Vol 3 (156) ◽  
pp. 35-40
Author(s):  
P. Gorbachov ◽  
O. Makarichev ◽  
O. Kolii ◽  
Y. Liubyi
Keyword(s):  
Traffic Flow ◽  
Delay Time ◽  
Regression Models ◽  
Basic Research ◽  
Transport Systems ◽  
Passenger Transportation ◽  
Flow Parameters ◽  
Object Of Study ◽  
Stop Point

The article is devoted to solving scientific and applied problems of determining the rational location of stopping points at the entrance or exit from controlled intersections. Analysis of approaches and methods to the determination of rational location of stopping points showed that they are mostly based on the goals of minimizing the time for passenger transportation or maximizing the performance of transport systems functioning. With that, the question of determining the time of delay of vehicle departure from the stopping point bottleneck after the embarkation and disembarkation of passengers is paid very little attention to. Currently, there are only regression models available that cannot claim to be universal and their use in transport planning requires similar conditions of functioning with the object, where statistic data were collected. The conducted analysis allowed determining the trend of basic research, namely, assessment of the influence of traffic flow parameters on the delay time of route transport departure from the stopping point bottleneck in the area adjacent to the controlled intersection. The process of delay occurrence at the exit of route transport from the stopping point bottleneck was formalized as the object of study thanks to which there was built an analytical model to determine the time of delay of route transport departure from the stopping point bottleneck. There were investigated two options for placement of a stopping point at the entrance and exit from the intersection. According to the results of calculations, it was determined that the delay time of route transport departure from the stopping point was influenced by many factors, whose influence varies depending on the location of the stopping point at the entrance and exit from a controlled intersection. By the results of researches one can be affirm that the most expedient is the placement of a stopping point at the minimum acceptable distance from the intersection, and it is recommended to locate a stopping point at a distance of 30 m at the entrance to the intersection. Keywords: stop, route vehicles, traffic flow, regulated intersections, traffic, latency, capacity transport areas.

scholarly journals Cytosolic delivery of inhibitory antibodies with cationic lipids

2019 ◽  
Vol 116 (44) ◽  
pp. 22132-22139 ◽  
Author(s):  
Hejia Henry Wang ◽  
Andrew Tsourkas
Keyword(s):  
Protein Function ◽  
Electrostatic Interactions ◽  
Efflux Pump ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Intracellular Protein ◽  
Cytosolic Delivery ◽  
Drug Efflux Pump ◽  
Inhibitory Antibodies ◽  
Delivery Efficiency

Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that IgG antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids originally designed for nucleic acid delivery through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs, enabling easy exchange of cargo IgGs. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes an approach for using existing antibody collections to modulate intracellular protein function.

Lipid anchoring and electrostatic interactions target NOT-LIKE-DAD to pollen endo-plasma membrane

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Laurine M. Gilles ◽  
Andrea R.M. Calhau ◽  
Veronica La Padula ◽  
Nathanaël M.A. Jacquier ◽  
Claire Lionnet ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Electrostatic Interactions ◽  
Membrane Surface ◽  
Male Gamete ◽  
Targeted Mutagenesis ◽  
Sperm Cells ◽  
Apical Region ◽  
Haploid Embryos ◽  
Membrane Surface Charge ◽  
Specific Membrane

Phospholipases cleave phospholipids, major membrane constituents. They are thus essential for many developmental processes, including male gamete development. In flowering plants, mutation of phospholipase NOT-LIKE-DAD (NLD, also known as MTL or ZmPLA1) leads to peculiar defects in sexual reproduction, notably the induction of maternal haploid embryos. Contrary to previous reports, NLD does not localize to cytosol and plasma membrane of sperm cells but to the pollen endo-plasma membrane (endo-PM), a specific membrane derived from the PM of the pollen vegetative cell that encircles the two sperm cells. After pollen tube burst, NLD localizes at the apical region of the egg apparatus. Pharmacological approaches coupled with targeted mutagenesis revealed that lipid anchoring together with electrostatic interactions are involved in the attachment of NLD to this atypical endo-PM. Membrane surface-charge and lipid biosensors indicated that phosphatidylinositol-4,5-bisphosphate is enriched in the endo-PM, uncovering a unique example of how membrane electrostatic properties can define a specific polar domain (i.e., endo-PM), which is critical for plant reproduction and gamete formation.

surgical experience with the modified blalock-taussig shunt: what we might learn from mathematical and laboratory studies?

2004 ◽  
Vol 14 (S3) ◽  
pp. 30-31 ◽  
Author(s):  
italo borini ◽  
maurizio marasini ◽  
giuseppe cervo ◽  
giovani calza ◽  
franco lerzo ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Fontan Operation ◽  
Complex Form ◽  
Basic Research ◽  
Systemic Circulation ◽  
Laboratory Studies ◽  
Surgical Experience ◽  
Caval Vein ◽  
Scientific Debate ◽  
Inferior Caval Vein

clinical experience in the treatment of patients with functionally univentricular hearts has shown the fontan operation to be much less than a perfect therapy. even in ideal patients, acquired elevation of the venous pressures in the systemic circulation, especially in the regions drained by the inferior caval vein, is only a matter of time. for this reason the treatment of this complex form of congenital heart disease is still the object of active scientific debate, as well as considerable ongoing medical and basic research.

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