Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nanoparticles are being increasingly used in consumer products worldwide, and their toxicological effects are currently being intensely debated. In vitro tests play a significant role in nanoparticle risk assessment, but reliable particle characterization in the cell culture medium with added fetal bovine serum (CCM) used in these tests is not available. As a step toward filling this gap, we report on silver ion release by silver nanoparticles and on changes in the particle radii and in their protein corona when incubated in CCM. Particles of a certified reference material, p1, and particles of a commercial silver nanoparticle material, p2, were investigated. The colloidal stability of p1 is provided by the surfactants polyethylene glycol-25 glyceryl trioleate and polyethylene glycol-20 sorbitan monolaurate, whereas p2 is stabilized by polyvinylpyrrolidone. Dialyses of p1 and p2 reveal that their silver ion release rates in CCM are much larger than in water. Particle characterization was performed with asymmetrical flow field-flow fractionation, small-angle X-ray scattering, dynamic light scattering, and electron microscopy. p1 and p2 have similar hydrodynamic radii of 15 and 16 nm, respectively. The silver core radii are 9.2 and 10.2 nm. Gel electrophoresis and subsequent peptide identification reveal that albumin is the main corona component of p1 and p2 after incubation in CCM that consists of Dulbecco's modified Eagle medium with 10% fetal bovine serum added.
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PMID:Characterization of Silver Nanoparticles in Cell Culture Medium Containing Fetal Bovine Serum. 2601 37

Several types of dialysis membranes have been developed in the history of hemodialysis therapy. Regenerated cellulose had been widely used for a long time, since the beginning of dialysis therapy. Regenerated cellulose is strongly hydrophilic, which enables lower membrane thickness and miniaturization of the dialyzer. The cellulose triacetate membrane has greater performance because of the lower thickness of the membrane and its lack of swelling due to high hydrophobicity. Many types of synthetic membranes, such as polysulfone, polyethersulfone and polyester polymer alloy membranes, have asymmetrical structures. Dialyzers with these membranes show higher capacities for water and solute transport because the actual membrane thickness, which is related to the water and solute transfer resistance, is quite small compared to that in membranes with homogeneous structures. The development of highly biocompatible membranes will be required in the future so as to prevent the development of adverse reactions and related complications. The performance of a dialyzer depends not only on the membrane permeability but also on the flow conditions of the blood and dialysate. Many types of dialyzers with high-performance membranes have been developed as a result of advances in membrane and device technologies. Recently, many types of high-flux dialyzers with high-performance membranes with a high internal filtration (IF)/backfiltration (BF) flow rate have been introduced. IF-enhanced hemodialysis using an enhanced IF dialyzer seems to be more convenient than hemodiafiltration therapy because it requires no additional equipment, such as a roller pump. In the near future, dialyzers should be developed with high capacities for the removal of low-molecular-weight proteins (LMWPs) related to complications and with low capacities for the loss of albumin and amino acid. Dialyzers with a sharp cut-off membrane between LMWPs and albumin and dialyzers with a special function, i.e., an adsorptive property for some LMWPs, are required. In addition, dialyzers with biocompatible membranes are necessary to prevent severe adverse reactions, although the causal relationship between these reactions and some complications are yet to be clarified.
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PMID:The past, present and future of the dialyzer. 2602 10

Liposomal delivery constitutes a promising approach for i.v. administration of temoporfin (mTHPC) because lipid membranes can host these drug molecules. This study investigates the transfer and release of mTHPC to plasma proteins and stability of various liposomal formulations. To this end, we employed traces of radioactive markers and studied the effects of fatty acid chain length and the degree of saturation in the lipophilic tail, addition of cholesterol and PEGylation of the membrane surface and different drug-to-lipid ratios (DLRs). Liposomes were incubated in human plasma for various incubation times. Drawn samples were separated by asymmetrical flow field-flow fractionation (AF4). Drug was recovered in four fractions identified as albumin, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and liposomes. Our results suggest that mTHPC fits best into fluid, unmodified bilayers when the drug-to-lipid ratio is low. Membrane rigidification as well as the presence of cholesterol and PEGyated lipids reduced the ability of the membrane to accommodate the drug but simultaneously improved the vesicle stability in plasma. Both mechanisms jointly affect the total degree of mTHPC release. We analyzed our data using a kinetic model that suggests the drug to be associated with the host membrane in two distinct states of which only one interacts directly with the plasma compartment.
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PMID:Investigations of the influence of liposome composition on vesicle stability and drug transfer in human plasma: a transfer study. 2775 Apr 73

An urgent challenge for imaging-guided disease-targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N-alkyl side chains to indocyanine green (ICG) (the only FDA-approved NIR contrast agent) are introduced, and a new analog, IR-DBI, is developed with simultaneous cancer-cell mitochondrial targeting, NIR imaging, and chemo-/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR-DBI a close binding to albumin protein site II to form a drug-protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR-DBI dye is further actively taken up by cancer cells through organic-anion-transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin-binding affinity, IR-DBI is modified into human serum albumin (HSA) via self-assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics.
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PMID:Structure-Guided Design and Synthesis of a Mitochondria-Targeting Near-Infrared Fluorophore with Multimodal Therapeutic Activities. 2898 Jul 31

In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal). Precise characterization was achieved in order to determine the amounts of lactose and Cyanine 5 (Cy5) coupled to the albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass greater than 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of the native albumin. In healthy mice, the accumulation of l-Cyal in the liver and its selectivity for hepatocyte cells were shown by optical imaging and flow cytometry. Administration of l-Cyal to mice bearing liver metastases showed a reduced signal in the liver related to a decrease in the number of hepatocytes. The l-Cyal bioimaging contrast agent could be particularly useful for assessing the state of liver related diseases.
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PMID:Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function. 3040 73

Vascular diseases are the main reason for morbidity and mortality worldwide. As we known, the earlier phase of vascular diseases is endothelial dysfunction in humans. The endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via the organizing of ligand-receptor associations and the various mediators' secretion. We can use many inflammatory non-invasive tests (flow-mediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and ankle-brachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von willebrand factor, endothelial microparticles and endothelial progenitor cells can be used to evaluate endothelial dysfunction. We have focused on the relation between endothelial dysfunction and inflammatory markers of vascular disease in this review.
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PMID:Endothelial dysfunction and inflammatory markers of vascular disease. 3231 94

Protein-based drugs often require targeted drug delivery for optimal therapy. A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). The results also indicate that the binding of GA-Z to HSA does not affect the ratio between HSA dimers and monomers, and that no higher order oligomers of the complex are seen other than those containing dimers of GA-Z and dimers of HSA.
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PMID:Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering. 3323 70


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