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albumin human [keywords]
- Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin. [JOURNAL ARTICLE]
- Eur J Med Chem 2014 Aug 24.:318-334.
A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.
- Physico-Chemical and Toxicological Characterisation of Iron-Containing Albumin Nanoparticles as Platforms for Medical Imaging. [JOURNAL ARTICLE]
- J Control Release 2014 Aug 27.
Iron oxide-containing magnetic nanoparticles (MNPs) have certain advantages over currently used contrast agents for tumor imaging by magnetic resonance imaging (MRI) as they offer the possibility of functionalization with ligands and tracers. Functionalized MNPs also may be used for targeted tumor therapy. In the current study nanoparticles (NPs) consisting of recombinant human serum albumin (rHSA) with incorporated hydrophilic (NH4)2Ce(IV)(NO3)6-γ-Fe2O3 particles (CAN maghemite particles) for medical imaging were produced and characterized. For this purpose CAN maghemite particles were incorporated into a rHSA matrix to yield rHSA-NPs. The resulting NPs were analysed by transmission electron microscopy, photon correlation spectroscopy, and atomic absorption. The sizes of the manufactured NP were 170±10nm, and the zeta-potential was -50±3mV. The NPs remained stable when stored after lyophilisation with sucrose 3% [w/v] as a cryoprotector. They showed pro-inflammatory properties without cell and animal toxicity in vivo and were highly contrasting in MRI. In conclusion, this report introduces novel rHSA NP with favourable properties containing iron oxide for detection by MRI.
- Orientational switching of protein conformation as a function of nanoparticle curvature and their geometrical fitting. [JOURNAL ARTICLE]
- J Chem Phys 2014 Aug 28; 141(8):084707.
Among the various surface properties, nanoparticle curvature has a direct effect on the inner root of protein nanoparticle interaction. However, the orientation of adsorbed proteins onto the nanoparticle surface and its binding mechanism still remains elusive because of the lack of in-depth knowledge at the molecular level. Here, we demonstrate detail molecular insights of the orientational switching of several serum proteins as a function of nanoparticle curvature using theoretical simulation along with some experimental results. With the variation of binding stability, four distinctly different classes of orientation were observed for human serum albumin, whereas only two unique classes of conformations were observed for ubiquitin, insulin, and haemoglobin. As a general observation, our data suggested that orientations were exclusively dependent on the specific protein structure and the geometrical fitting onto the nanoparticle surface.
- Interaction of chlorogenic acids and quinides from coffee with human serum albumin. [JOURNAL ARTICLE]
- Food Chem 2015 Feb 1.:332-340.
Chlorogenic acids and their derivatives are abundant in coffee and their composition changes between coffee species. Human serum albumin (HSA) interacts with this family of compounds with high affinity. We have studied by fluorescence spectroscopy the specific binding of HSA with eight compounds that belong to the coffee polyphenols family, four acids (caffeic acid, ferulic acid, 5-O-caffeoyl quinic acid, and 3,4-dimethoxycinnamic acid) and four lactones (3,4-O-dicaffeoyl-1,5-γ-quinide, 3-O-[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide, 3,4-O-bis[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide, and 1,3,4-O-tris[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide), finding dissociation constants of the albumin-chlorogenic acids and albumin-quinides complexes in the micromolar range, between 2 and 30μM. Such values are comparable with those of the most powerful binders of albumin, and more favourable than the values obtained for the majority of drugs. Interestingly in the case of 3,4-O-dicaffeoyl-1,5-γ-quinide, we have observed the entrance of two ligand molecules in the same binding site, leading up to a first dissociation constant even in the hundred nanomolar range, which is to our knowledge the highest affinity ever observed for HSA and its ligands. The displacement of warfarin, a reference drug binding to HSA, by the quinide has also been demonstrated.
- Highly sensitive electrochemical aptasensor for immunoglobulin E detection based on sandwich assay using enzyme linked aptamer. [JOURNAL ARTICLE]
- Anal Biochem 2014 Aug 26.
Here, we described the fabrication of an electrochemical immunoglobulin-E(IgE) aptasensor using enzyme linked aptmer in sandwich assay method and thionine as redox probe. In this protocol,5'-amine-terminated IgE aptamer and thionine were covalently attached on glassy carbon electrode modified with carbon nanotubes/ionic liquid/chitosan nanocomposite. Furthermore, another IgE aptamer was modified with biotin and enzyme horseradish peroxidase(HRP) which attached to the aptamer via biotin-streptavidin interaction. Electrochemical impedance spectroscopy(EIS) and cyclic voltammetry were performed at each stage of the chemical modification process in order to confirm the resulting surface changes. The presence of IgE induces the formation of a double aptamer sandwich structure on the electrode and the electrocatalytic reduction current of thionine in the presence of hydrogen peroxide was measured as sensor response. Under optimized condition and using differential pulse voltammetry as measuring technique the proposed aptasensor showed low detection limit(6 pM) and high sensitivity 1.88μAnM(-1). This aptasensor also exhibit good stability and high selectivity for IgE detection without interfering effect of some other proteins such as bovine serum albumin(BSA) and lysozyme. The application of the aptasensor for IgE detection in human serum sample is also investigated. The proposed protocol is quite promising as alternative sandwich approach for various protein assays.
- Protein-phenolic interactions and inhibition of glycation - combining a systematic review and experimental models for enhanced physiological relevance. [JOURNAL ARTICLE]
- Food Funct 2014 Aug 29.
Background: while antiglycative capacity has been attributed to (poly)phenols, the exact mechanism of action remains unclear. Studies so far are often relying on supra-physiological concentrations and use of non-bioavailable compounds. Methods: to inform the design of a physiologically relevant in vitro study, we carried out a systematic literature review of dietary interventions reporting plasma concentrations of polyphenol metabolites. Bovine Serum Albumin (BSA) was pre-treated prior to in vitro glycation: either no treatment (native), pre-oxidised (incubated with 10 nM H2O2, for 8 hours) or incubated with a mixture of phenolic acids at physiologically relevant concentrations, for 8 hours). In vitro glycation was carried out in the presence of (i) glucose only (0, 5 or 10 mM), (ii) glucose (0, 5 or 10 mM) plus H2O2 (10 nM), or (iii) glucose (0, 5 or 10 mM) plus phenolic acids (10-160 nM). Fructosamine was measured using the nitro blue tetrazolium method. Results: following (high) dietary polyphenol intake, 3-hydroxyphenylacetic acid is the most abundant phenolic acid in peripheral blood (up to 338 μM) with concentrations of other phenolic acids ranging from 13 nM to 200 μM. The presence of six phenolic acids with BSA during in vitro glycation did not lower fructosamine formation. However, when BSA was pre-incubated with phenolic acids, significantly lower concentration of fructosamine was detected under glycoxidative conditions (glucose 5 or 10 mM plus H2O2 10 nM) (p < 0.001 vs. native BSA). Conclusion: protein pre-treatment, either with oxidants or phenolic acids, is an important regulator of subsequent glycation in a physiologically relevant system. High quality in vitro studies under conditions closer to physiology are feasible and should be employed more frequently.
- Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy. [Journal Article, Review]
- World J Radiol 2014 Aug 28; 6(8):598-606.
In single photon emission computed tomography-based three-dimensional radiotherapy (SPECT-B-3DCRT), images of Tc-99m galactosyl human serum albumin (GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation images. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepatocellular carcinoma (HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none experienced fatal radiation-induced liver disease (RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients given doses of ≥ 20 Gy (FLV20Gy). Therefore, FLV20Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20Gy as a qualitative index, we propose a quantitative indicator, F 20Gy, which was calculated as F 20Gy = 100% × (the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).
- Dynamic contrast-enhanced(DCE) MRI Assessment of microvascular characteristics in the murine orthotopic pancreatic cancer model. [JOURNAL ARTICLE]
- Magn Reson Imaging 2014 Aug 25.
Object To assess the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters between two contrast agents in a murine orthotopic pancreatic cancer model and to evaluate the tumor heterogenity and the potential association between kinetic parameters and angiogenic markers such as the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry.Human pancreatic adenocarcinoma cell line MIAPaCa-2 was injected into the pancreas of BALB/C nu/nu mice. DCE-MRI was performed using Gd-DTPA and Gd-EOB-DTPA. Quantitative and semi-quantitative vascular parameters (K(trans), Kep, Ve and AUC) were calculated by using a dedicated postprocessing software program.Values were compared with tumor rim, tumor core and the entire tumor. The MVD and VEGF expression between tumor rim and tumor core were also compared.There were no significant differences in K(trans), Kep, Ve, and AUC values of the three groups when using Gd-DTPA. But there were significant differences in K(trans), Kep, and AUC values of the three groups when using Gd-EOB-DTPA (P=0.014, 0.022, 0.007, respectively), in addition, the K(trans) and Kep values of tumor core were significantly lower than those of the entire tumor (adjusted P=0.014 and 0.027, respectively), the AUC values of core were significantly lower than those of the entire tumor and rim (adjusted P=0.039 and 0.009, respectively). Immunohistology results revealed that MVD and VEGF expression in the tumor rim was significantly higher than that in the core. There was positive correlation between AUC and MVD, VEGF.The murine orthotopic pancreatic cancer model provides an ideal animal model to study human pancreatic cancer. It can more sensitively semi-quantitatively and quantitatively analyze tumor angiogenesis through selecting the albumin-binding contrast agent.
- Inflammatory cell recruitment after experimental thromboembolic stroke in rats. [JOURNAL ARTICLE]
- Neuroscience 2014 Aug 25.
Inflammatory mechanisms were recently identified as contributors to delayed neuronal damage after ischemic stroke. However, therapeutic strategies are still lacking, probably related to the outstanding standardization on inflammatory cell recruitment emerging from predominantly artificial stroke models, and the uncertainty on functional properties of distinct subpopulations. Using a rodent model of stroke that closely reflects human embolic ischemia, this study was focused on the local recruitment of immunoreactive cells as well as their functional and regional characterization. Wistar rats underwent thromboembolic middle cerebral artery occlusion, followed by intravenous injection of the blood-brain barrier permeability marker FITC-albumin at 24 hours. One hour later, brain tissue was subjected to multi-parameter flow cytometry and Pappenheim staining to characterize cells invaded into the ischemia-affected hemisphere, compared to the contralateral side. Immunofluorescence labeling was applied to explore the distribution patterns of recruited cells and their spatial relationships with the vasculature. One day after ischemia onset, a 6.12-fold increase of neutrophils and a 5.43-fold increase of monocytes/macrophages was found in affected hemispheres, while these cells exhibited enhanced MHC class II expression and allocation with vessels exhibiting impaired blood-brain barrier integrity. Microglia remained numerically unaltered in ischemic hemispheres, but shifted to an activated phenotype indicated by CD45/CD86 expression and morphological changes towards an ameboid appearance in the bordering zone. Ischemia caused an increase of lymphoid cells in close vicinity to the affected vasculature, while further analyses allowed separation into NK cells, NKT cells, T cells (added by an unconventional CD11b(+)/CD3(+) population) and 2 subpopulations of B cells. Taken together, our study provides novel data on the local inflammatory response to experimental thromboembolic stroke. As concomitantly present neutrophils, monocytes/macrophages and lymphoid cells in the early stage after ischemia induction correspond to changes seen in human stroke, future stroke research should preferably use animal models with relevance for clinical translation.
- Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease. [JOURNAL ARTICLE]
- J Inherit Metab Dis 2014 Aug 28.
Patients with glycogen storage diseases type 1 (GSD1) suffer from life-threatening hypoglycaemia, when left untreated. Despite an intensive dietary treatment, patients develop severe complications, such as liver tumors and renal failure, with aging. Until now, the animal models available for studying the GSD1 did not survive after weaning. To gain further insights into the molecular mechanisms of the disease and to evaluate potential treatment strategies, we have recently developed novel mouse models in which the catalytic subunit of glucose-6 phosphatase (G6pc) is deleted in each glucose-producing organ specifically. For that, B6.G6pc(ex3lox/ex3lox) mice were crossed with transgenic mice expressing a recombinase under the control of the serum albumin, the kidney androgen protein or the villin promoter, in order to obtain liver, kidney or intestine G6pc(-/-) mice, respectively. As opposed to total G6pc knockout mice, tissue-specific G6pc deficiency allows mice to maintain their blood glucose by inducing glucose production in the other gluconeogenic organs. Even though it is considered that glucose is produced mainly by the liver, liver G6pc(-/-) mice are perfectly viable and exhibit the same hepatic pathological features as GSD1 patients, including the late development of hepatocellular adenomas and carcinomas. Interestingly, renal G6pc(-/-) mice developed renal symptoms similar to the early human GSD1 nephropathy. This includes glycogen overload that leads to nephromegaly and morphological and functional alterations in the kidneys. Thus, our data suggest that renal G6Pase deficiency per se is sufficient to induce the renal pathology of GSD1. Therefore, these new mouse models should allow us to improve the strategies of treatment on both nutritional and pharmacological points of view.