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#29045929   2017/10/18 Save this To Up

Deciphering the complexation process of a fluoroquinolone antibiotic, levofloxacin, with bovine serum albumin in the presence of additives.

The current work aims to explore the thermodynamic and conformational aspects for the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible, fluorescence, circular dichroism, and (1)H NMR), dynamic light scattering (DLS) and computational methods (molecular docking). The binding of LFC with BSA at two sequential sites with higher affinity (~10(3)M(-1)) at the first site has been explored by calorimetry whereas the binding at a single site with affinity of the order of ~10(4)M(-1) has been observed from fluorescence spectroscopy. The calorimetric study in the presence of additives along with docking analysis reveals the significant role of electrostatic, hydrogen bonding, and hydrophobic interactions in the association process. The slight conformational changes in protein as well as the changes in the water network structure around the binding cavity of protein have been observed from spectroscopic and DLS measurements. The LFC induced quenching of BSA fluorescence was observed to be initiated mainly through the static quenching process and this suggests the formation of ground state LFC-BSA association complex. The stronger interactions of LFC in the cavity of Sudlow site I (subdomain IIA) of protein have been explored from site marker calorimetric and molecular docking study.

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Bovine Serum Albumin (BSA Thermal Shaker with cooli FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Multiple organ tumor tiss Bovine serum albumin Bovine serum albumin Anti Anti-Bovine Serum Albumin

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#29042926   2017/10/18 Save this To Up

Anti-EGFR antibody conjugated silica nanoparticles as probes for lung cancer detection.

A well-designed nanosystem [anti-epidermal growth factor receptor-MB-encapsulated thiol-terminated silica nanoparticles (EGFR/MB-SHSi) complexes] containing silica nanoparticles and near-infrared fluorescence dye (NIRF) methylene blue (MB) was established as a tumor-targeted probe for potential lung cancer detection. The anti-EGFR/MB-SHSi complexes exhibited desirable and homogenous particle size, high bovine serum albumin stability, low hemolytic activity, neutral surface charges and negligible cytotoxicity in vitro. Furthermore, the results of confocal laser scanning microscopy and flow cytometry confirmed that the EGFR-targeted function induced high and specific cellular uptake of anti-EGFR/MB-SHSi complexes. In vivo investigation of nude mice bearing A549 tumor xenografts revealed that anti-EGFR/MB-SHSi complexes possessed strong tumor target ability. These observations indicated that anti-EGFR/MB-SHSi complexes may be a safe and tumor-targeting probe for the detection of cancer.

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#29042638   2017/10/18 Save this To Up

Carbon nanowalls as a platform for biological SERS studies.

Herein we report about developing new type of Surface Enhanced Raman Scattering (SERS) substrates based on Au-decorated carbon nanowalls. The designed substrates possess high specific surface area and high sensitivity. Chemical stability of Au perfectly blends with electrical properties and high value of specific surface area of carbon nanowalls. Created structures were applied to detect signals of a typical molecule used for SERS substrates testing, rhodamine 6G, which exhibits electronic absorption in the visible area of spectrum, and biomacromolecules such as tryptophan, guanine, bovine serum albumin and keratin hydrolysates, whose electronic absorption is in the ultraviolet region of spectrum and lies far from the Au plasmonic resonance. The obtained signals for these compounds suggest that the developed substrate is a prominent platform for the detection of biological macromolecules. The properties of the substrate, including its morphology and Au film thickness, as well as the analyte deposition method, were optimized to achieve the optimum Raman signal enhancement. Electric field distribution in the designed structures was calculated to describe the observed dependence of SERS activity on the substrate morphology.

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#29042337   2017/10/18 Save this To Up

PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium.

Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual mTOR/PI3K inhibitor that is of potential interest in the treatment of inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric nanoparticles composed of a blend of poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-2000 (PLGA-PEG). The nanoparticles were prepared by an oil/water emulsion solvent evaporation method, and were subsequently characterized for yield, encapsulation efficiency, morphology, particle size, drug-polymer interaction and in vitro drug release profiles. A targeted formulation was developed by conjugation of a S-acetyl-thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The particle size distribution showed a range from 250 to 360nm with a high (>75%) BEZ encapsulation efficiency. Approximately 35% of the loaded BEZ was released within 10days at 37°C in a medium containing 5% bovine serum albumin (BSA). Evaluation of efficacy of anti-E-selectin decorated BEZ-loaded nanoparticles was carried out in tumor necrosis factor-α (TNF-α) activated endothelial cells. Confocal microscopy analysis showed that cellular uptake of the targeted nanoparticles and subsequent internalization. Cell functional assays, including migration assay and phosphowestern blot analysis of the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated endothelial cells as compared to the non-targeted BEZ-loaded nanoparticles. In conclusion, E-selectin targeted nanoparticles have a high potential in delivering the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are an interesting nanomedicine for anti-inflammatory therapy.

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mTOR Inhibitor, Ku 006379 mTOR Inhibitor, Ku 006379 BEZ-235 Mechanisms: PI3K XL-765 (SAR-245409) Mecha GDC-0980 Mechanisms: PI3K BGT-226 Mechanisms: PI3K PKI-587 (PF-05212384) Mec PF-04691502 Mechanisms: P FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu

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#29042238   2017/10/18 Save this To Up

Novel strategy for immunomodulation: dissolving microneedle array encapsulating thymopentin fabricated by modified two-step molding technology.

Thymopentin (TP5) is commonly used in the treatment for autoimmune diseases, with a short plasma half-life (30 s) and a long treatment period (7 days to 6 months). It is usually administrated by syringe injection, resulting in compromised patient compliance. Dissolving microneedle array (DMNA) offers a superior approach for transdermal delivery of biological macromolecules, as it allows painless penetration through the stratum corneum and generates minimal biohazardous waste after dissolving in the skin. Despite recent advances in DMNA as a novel approach for transdermal drug delivery, problem of insufficient mechanical strength remains to be solved. In this study, TP5-loaded DMNA (TP5-DMNA) was uniquely developed using a modified two-step molding technology. The higher mechanical strength was furnished by employing bovine serum albumin (BSA) as a co-material to fabricate the needles. The obtained TP5-DMNA containing BSA displayed better skin penetration and higher drug loading efficiency than that without BSA. The in vivo pharmacodynamics study demonstrated that TP5-DMNA had comparative effect on immunomodulation to intravenous injection of TP5, in terms of ameliorating the CD4+/CD8+ ratio, SOD activity and MDA value to the basal level. Only mild irritation was observed at the site of administration. These results suggest that the novel TP5-DMNA utilizing BSA provides an alternative approach for convenient and safe transdermal delivery of TP5, which is a promising administration strategy for future clinical application.

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#29042133   2017/10/18 Save this To Up

Determination of mitochondrial metabolic phenotype through investigation of the intrinsic inhibition of succinate dehydrogenase.

Many diseases are accompanied by systemic or organ metabolic abnormalities. Therefore, investigation of the roles of mitochondrial dysfunction in the pathogenesis of major diseases requires a methodology that reflects the characteristics of mitochondrial metabolism particular for the organ of origin. We provide evidence that for brain and heart mitochondria the intrinsic inhibition of succinate dehydrogenase (SDH) is a key mechanism for attenuation of mitochondrial respiration and energy production in response to the organ's energy needs. This mechanism also serves to minimize the production of reactive oxygen species when the organ is at rest. Changes in the organ's workloads are accompanied by changes in metabolites that are used by mitochondria as substrates and for modification of energy production at the SDH level. Measurement of the respiratory activity of mitochondria with various substrates and substrate mixtures and use of bovine serum albumin as an SDH inhibitorwill be useful for evaluation of metabolic phenotype at the mitochondrial level.

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Ofloxacin CAS Number [824 QuantiChrom™ LDH Cytoto Lactate dehydrogenase A Lactate dehydrogenase D Isocitrate Dehydrogenase Isocitrate Dehydrogenase BACTERIOLOGY BACTEROIDES EIA for Quantitative Dete EIA for Quantitative Dete Goat Anti-Human pan-Alcoh VDAC1 - Rabbit polyclonal FluoroQuest™ Fluorescen

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#29039485   2017/10/17 Save this To Up

Calcium dobesilate may alleviate diabetes‑induced endothelial dysfunction and inflammation.

Diabetic kidney disease (DKD) is a leading cause of end‑stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D‑glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit‑8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)‑labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)‑1, monocyte chemotactic protein (MCP)‑1 and pentraxin‑related protein (PTX3)] was evaluated via reverse transcription‑quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM‑1, MCP‑1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time‑dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG‑treated HUVECs exhibited increased FITC‑BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG‑induced increase in FITC‑BSA permeability and suppressed HG‑induced overexpression of endothelial markers (VEGF, VEGFR‑2, endocan) and inflammation markers (ICAM‑1, MCP‑1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG‑induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.

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#29037721   2017/10/17 Save this To Up

Thermodynamic and kinetic analyses of curcumin and bovine serum albumin binding.

Bovine serum albumin (BSA)/curcumin binding and dye photodegradation stability were evaluated. BSA/curcumin complex showed 1:1 stoichiometry, but the thermodynamic binding parameters depended on the technique used and BSA conformation. The binding constant was of the order of 10(5)L·mol(-1) by fluorescence and microcalorimetric, and 10(3) and 10(4)L·mol(-1) by surface plasmon resonance (steady-state equilibrium and kinetic experiments, respectively). For native BSA/curcumin, fluorescence indicated an enthalpic and entropic driven process based on the standard enthalpy change (ΔH(○)F=-8.67kJ·mol(-1)), while microcalorimetry showed an entropic driven binding process (ΔH(○)cal=29.11kJ·mol(-1)). For the unfolded BSA/curcumin complex, it was found thatp ΔH(○)F=-16.12kJ·mol(-1) and ΔH(○)cal=-42.63kJ·mol(-1). BSA (mainly native) increased the curcumin photodegradation stability. This work proved the importance of using different techniques to characterize the protein-ligand binding.

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Bovine Androstenedione,AS Bovine Serum Albumin (BSA Rabbit Anti-Rat Androgen Bovine serum albumin Bovine serum albumin Anti Anti-Bovine Serum Albumin Anti Bovine Serum Albumin Anti-Bovine Serum Albumin Monoclonal Anti-Bovine Se Monoclonal Anti Bovine Se BSA | bovine serum albumi BSA | bovine serum albumi

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#29037116   2017/10/17 Save this To Up

Relating physicochemical properties of alginate-HMP complexes to their performance as drug delivery systems.

This study aims to analyze the effect of physicochemical properties of alginate-high methoxyl pectin (HMP)complexes on their performance as drug delivery systems.Rheology, textural propertiesand swelling behavior of alginate-HMP complexes were determined. HMP alone showed weak gelling ability.As ratio of alginate increased, gel capability, hardness and adhesiveness of gels increased, but swelling rate decreased. Bovine serum albumin (BSA) was used as a model drug and entrapped in the alginate-HMP beads. Morphology of beads was correlated with adhesiveness. Drug loading content and encapsulation efficiency were related to electrostatic interactions between BSA and alginate-HMP complexes. Drug release profiles were correlated with both texture and swelling properties of alginate-HMP complexes and morphology of beads in simulated gastric fluids, while release in simulated intestinal fluids was affected by drug loading content. This study gives enlightenment that pre-selection of encapsulation materials may be achieved prior to encapsulation based on physicochemical properties of materials.

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#29033982   2017/10/16 Save this To Up

Effects of multiwalled carbon nanotube surface modification and purification on bovine serum albumin binding and biological responses.

The potential diagnostic and therapeutic applications such as drug delivery of multi-walled carbon nanotubes (MWCNTs) are being increasingly explored due to their unique mechanical, chemical and biological properties. Carboxylation of MWCNTs has been widely used to improve the solubility in aqueous systems, and for further functionalization with biologically active moieties. Purity of carboxylated MWCNTs is of great importance in nanomedicine. An important consideration is that oxidation debris is generated during the process of carboxylation, which can be removed by base washing. We hypothesized that surface modification as well as further purification by debris removal may alter physicochemical properties of MWCNTs and their ability to bind proteins. In this study, we utilized pristine MWCNT carboxylated MWCNTs (F-MWCNTs) and base-washed carboxylated MWCNTs (BW-F-MWCNTs) to examine formation of a bovine serum albumin (BSA) protein corona and impact on biological responses. We found that carboxylation increased the capability of F-MWCNTs to bind BSA, and base washing further increased this binding by 41% implying that purification of F-MWCNTs is an important consideration in biological applications. The BSA protein corona decreased the hydrodynamic size of MWCNTs by nearly 50% because the coating improved colloidal behavior. The effect was significantly less pronounced for F-MWCNTs and BW-F-MWCNTs because they were highly dispersible to begin with. Functionalization increased cellular uptake by both rat aortic endothelial cells (RAEC) and macrophage-like murine cells (RAW264.7), while base washing showed results similar to the functionalized analog. Interestingly, BSA binding downregulated mRNA levels of interleukin-6 (IL-6) and heme oxygenase 1 (Hmox1) in RAEC cells but upregulated the expression of IL-6 and Hmox1 in RAW264.7 cells, indicating the dependence of cell types in biological responses to MWCNTs. Overall, our study demonstrated that surface modification as well as further purification impacted the interaction of MWCNTs with proteins and subsequent cellular responses. Interestingly, while the corona associated with the F-MWCNTs and BW-F-MWCNTs were significantly different, their respective cellular uptake and biological responses were similar. This implied that surface functionalization played a more important role than surface corona.

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Bovine Androstenedione,AS Bovine Serum Albumin (BSA Rabbit Anti-Rat Androgen Bovine serum albumin Bovine serum albumin Anti Anti-Bovine Serum Albumin Anti Bovine Serum Albumin Anti-Bovine Serum Albumin Monoclonal Anti-Bovine Se Monoclonal Anti Bovine Se BSA | bovine serum albumi BSA | bovine serum albumi

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