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#32473371   2020/05/27 To Up

Bioresponsive nanostructured systems for sustained naltrexone release and treatment of alcohol use disorder: development and biological evaluation.

In this study, microemulsions capable of transforming into nanostructured hexagonal phase gels in vivo upon uptake of biological fluids for naltrexone prolonged release were investigated as a strategy for management of alcohol use disorder (AUD). Microemulsions were prepared using monoolein, tricaprylin, water and propylene glycol; after preliminary characterization, one formulation was selected, which contained 55% of monoolein-tricaprylin (M-55). This microemulsion displayed size below 200 nm and Newtonian rheological behavior. Liquid crystalline gels formed in vitro upon 8 h of contact with water following a second order kinetics. After 120 h, less than 50% of naltrexone was released in vitro independently on drug loading (5 or 10%). In vivo, gels formed within 24 h of M-55 subcutaneous administration, and persisted locally for over 30 days providing slow release of the fluorescent marker Alexa fluor compared to a solution. Using the conditioned place preference paradigm, a test used to measure drug's rewarding effects, a single dose of M-55 containing 5% naltrexone reduced the time spent in the ethanol-paired compartment by 1.8-fold compared to saline; this effect was similar to that obtained with daily naltrexone injections, demonstrating the formulation efficacy and its ability to reduce dosing frequency. A more robust effect was observed following administration of M-55 containing 10% of naltrexone, which was compatible with aversion. These results support M-55 as a platform for sustained release of drugs that can be further explored for management of AUD to reduce dosing frequency and aid treatment adherence.
Rogério A Santos, Mariana Rae, Vanessa F M C Dartora, Jenyffer K R Matos, Rosana Camarini, Luciana B Lopes

1320 related Products with: Bioresponsive nanostructured systems for sustained naltrexone release and treatment of alcohol use disorder: development and biological evaluation.

25 mg 5 G 5 G1 g100ug96 wells (1 kit)50 ug 200ul100.00 ul10 mg100 mg5mg

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#32472426   2020/05/29 To Up

Effect of the usage of Er,Cr:YSGG laser with and without different remineralization agents on the enamel erosion of primary teeth.

The aim of the present study was to evaluate the effects of different remineralization agents associated with erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) (0.5 W power, 20 Hz frequency, 60% water, 40% air, 25 mJ pulse energy, 8.84 J/cm fluence, 60 μs pulse duration, 600 μm tip diameter, and an approximate 1-1.5 mm distance to the target) laser irradiation on erosion induced by the consumption of carbonated drinks in human primary enamel. There were 8 groups and 10 primary teeth in each g0roup. The distribution was as follows: group 1, casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF); group 2, Er,Cr:YSGG laser+CPP-ACPF; group 3, fluor varnish; group 4, Er,Cr:YSGG Laser+fluoride varnish; group 5, ROCS® medical mineral gel; group 6, Er,Cr:YSGG laser + ROCS® medical mineral gel; group 7, Er,Cr:YSGG laser; and group 8, artificial saliva. The samples in the groups were submerged in artificial saliva and acid twice a day for 6 s at 6-h intervals and were then exposed to an erosion cycle 15 times. In the groups in which the Er,Cr:YSGG laser was applied in combination with the remineralization agents, the laser application was made first, and then the remineralization agents were applied for 4 min in each group. The Friedman and Wilcoxon signed-rank tests and the Bonferroni correction were used in statistical analyses, and the significance level was taken as p < 0.05. According to the results, all agents had a statistically significant difference (groups 1, 2, 3, 4, and 6: p = 0.005, p < 0.017; groups 5 and 7: p = 0.007, p < 0.017) between BL-RM periods. However, all agents had a statistically significant remineralization effect on primary teeth enamel (groups 1, 2, 3, 6, and 7: p = 0.005, p < 0.017; group 4: p = 0.011, p < 0.017) except that group 5 (p = 0.074, p < 0.017) between DM-RM periods. The coadministration of an agent with the laser did not make any difference at a statistical level (p = 0.804, p > 0.05). The results were supported by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. As a result of this study, CPP-ACPF had a notable impact in terms of the remineralization effect on eroded enamel, and the Er,Cr:YSGG laser alone may be an alternative method, which may be related to the modified hydroxyapatite structure, 38.5% HCaOPY, that was determined in XRD analysis.
Nagehan Yilmaz, Ezgi Baltaci, Ozgul Baygin, Tamer Tüzüner, Serdar Ozkaya, Aykut Canakci

2037 related Products with: Effect of the usage of Er,Cr:YSGG laser with and without different remineralization agents on the enamel erosion of primary teeth.

5 G100.1 mg 100 G100 IU1500 Units2

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#32470633   2020/05/06 To Up

Integrated super resolution fluorescence microscopy and transmission electron microscopy.

In correlative light and electron microscopy (CLEM), the capabilities of fluorescence microscopy (FM) and electron microscopy (EM) are united. FM combines a large field of view with high sensitivity for detecting fluorescence, which makes it an excellent tool for identifying regions of interest. EM has a much smaller field of view but offers superb resolution that allows studying cellular ultrastructure. In CLEM, the potentials of both techniques are combined but a limiting factor is the large difference in resolution between the two imaging modalities. Adding super resolution FM to CLEM reduces the resolution gap between FM and EM; it offers the possibility of identifying multiple targets within the diffraction limit and can increase correlation accuracy. CLEM is usually carried out in two separate setups, which requires transfer of the sample. This may result in distortion and damage of the specimen, which can complicate finding back regions of interest. By integrating the two imaging modalities, such problems can be avoided. Here, an integrated super resolution correlative microscopy approach is presented based on a wide-field super resolution FM integrated in a Transmission Electron Microscope (TEM). Switching imaging modalities is accomplished by rotation of the TEM sample holder. First imaging experiments are presented on sections of Lowicryl embedded Human Umbilical Vein Endothelial Cells labeled for Caveolin both with Protein A-Gold, and Alexa Fluor®647. TEM and FM images were overlaid using fiducial markers visible in both imaging modalities with an overlay accuracy of 28 ± 11 nm. This is close to the optical resolution of ~50 nm.
Sajjad Mohammadian, Alexandra V Agronskaia, Gerhard A Blab, Elly G van Donselaar, Cecilia de Heus, Nalan Liv, Judith Klumperman, Hans C Gerritsen

1450 related Products with: Integrated super resolution fluorescence microscopy and transmission electron microscopy.

100ug Lyophilized100ug Lyophilized1 kit25 mg1 kit100 ul1 kit100 umoles 125 ml 1 kit10 mg1 kit

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#32465842   2020/03/30 To Up

C-Kit-Derived CD11b Cells are Critical for Cardiac Allograft Prolongation by Autologous C-Kit Progenitor Cells.

Published results show that autologous C-Kit cells robustly prolong cardiac allografts in a C-Kit and dose-dependent fashion. To extend our understanding, we determined if the allograft protective effects of C-Kit cells were preserved under conditions of immune suppression, what the primary signal for differential engraftment of the allograft and related immune tissues by C-Kit-derived cells was, and the class of C-kit-derived cells responsible for allograft prolongation.
T J Grazia, R J Plenter, M G Coulombe, C M Lin, R G Gill, M R Zamora

1147 related Products with: C-Kit-Derived CD11b Cells are Critical for Cardiac Allograft Prolongation by Autologous C-Kit Progenitor Cells.

1.00 flask4 x 96-well plate1.00 flask0.1ml (1mg/ml)1 ml15ml10 assays200 1mg 1 kit(s) 1x10e7 cells25ml

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#32454402   2020/05/23 To Up

CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model.

The completeness of resection is a key prognostic indicator in patients with ovarian cancer, and the application of tumour-targeted fluorescence image-guided surgery (FIGS) has led to improved detection of peritoneal metastases during cytoreductive surgery. CD24 is highly expressed in ovarian cancer and has been shown to be a suitable biomarker for tumour-targeted imaging.
Katrin Kleinmanns, Vibeke Fosse, Ben Davidson, Elvira García de Jalón, Olav Tenstad, Line Bjørge, Emmet McCormack

1658 related Products with: CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model.

1 kit1 kit

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#32454401   2020/05/23 To Up

CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma.

The survival rate of patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains disappointing. Clinically translatable orthotopic cell line xenograft models and patient-derived xenografts (PDXs) may aid the implementation of more personalised treatment approaches. Although orthotopic PDX reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by lack of appropriate imaging modalities.
Katrin Kleinmanns, Katharina Bischof, Shamundeeswari Anandan, Mihaela Popa, Lars A Akslen, Vibeke Fosse, Ida Tveit Karlsen, Bjørn T Gjertsen, Line Bjørge, Emmet McCormack

1412 related Products with: CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma.



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#32444494   2020/05/22 To Up

The Cyt1Aa toxin from Bacillus thuringiensis inserts into target membranes via different mechanisms in insects, red blood cells, and lipid liposomes.

Bacillus thuringiensis subsp. israelensis (Bti) produces crystal inclusions composed of three-domain Cry proteins and cytolytic Cyt toxins, which are toxic to different mosquito larvae. A key component is the Cyt toxin, which synergizes the activity of the other Cry toxins, thereby resulting in high toxicity. The precise mechanism of action of Cyt toxins is still debated, and two models have been proposed, the pore formation model and the detergent effect. Here, we performed a systematic structural characterization of the Cyt toxin interaction with different membranes, including in Aedes aegypti larval brush border membrane vesicles (BBMVs), small unilamellar vesicles (SUVs) liposomes, and rabbit erythrocytes. We examined Cyt1Aa insertion into these membranes by analyzing fluorescence quenching in solution and in the membrane-bound state. For this purpose, we constructed several Cyt1Aa variants having substitutions with a single cysteine residue in different secondary structures, enabling Cys labeling with Alexa Fluor-488 for quenching analysis using I-soluble quencher in solution and in the membrane-bound state. We identified the Cyt1Aa residues exposed to the solvent upon membrane insertion, predicting a possible topology of the membrane-inserted toxin in the different membranes. Moreover, toxicity assays with these variants revealed that Cyt1Aa exerts its insecticidal activity and hemolysis through different mechanisms. We found that Cyt1Aa exhibits variable interactions with each membrane system, with deeper insertion into mosquito larva membranes, supporting the pore formation model, whereas in the case of erythrocytes and SUVs, Cyt1Aa's insertion was more superficial, supporting the notion that a detergent effect underlies its hemolytic activity.
Janette Onofre, Sabino Pacheco, Mary Carmen Torres-Quintero, Sarjeet S Gill, Mario Soberon, Alejandra Bravo

1005 related Products with: The Cyt1Aa toxin from Bacillus thuringiensis inserts into target membranes via different mechanisms in insects, red blood cells, and lipid liposomes.

10 ug0.1ml (1mg/ml)1 mg5mg15ml5mg4 Membranes/Box15ml100 5mg

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#32428684   2020/05/16 To Up

Biocompatibility and Bioactivity of an FGF-Loaded Microsphere-Based Bilayer Delivery System.

Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation.
Dong Hwa Kim, Julianne Huegel, Brittany L Taylor, Courtney A Nuss, Stephanie N Weiss, Louis J Soslowsky, Robert L Mauck, Andrew F Kuntz

2278 related Products with: Biocompatibility and Bioactivity of an FGF-Loaded Microsphere-Based Bilayer Delivery System.

70 Slides 500 MG50 ug 500 Slides 25 mg10 mg 1 kit(s) 96T 70 Slides 50 mg100ug

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#32400834   // To Up

Effect of a post-translational modification mimic on protein translocation through a nanopore.

Post-translational modifications (PTMs) of proteins are recognized as crucial components of cell signaling pathways through modulating folding, altering stability, changing interactions with ligands, and, therefore, serving multiple regulatory functions. PTMs occur as covalent modifications of the protein's amino acid side chains or the length and composition of their termini. Here we study the functional consequences of PTMs for α-synuclein (αSyn) interactions with the nanopore of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. PTMs were mimicked by a divalent Alexa Fluor 488 sidechain attached separately at two positions on the αSyn C-terminus. Using single-channel reconstitution into planar lipid membranes, we find that such modifications change interactions drastically in both efficiency of VDAC inhibition by αSyn and its translocation through the VDAC nanopore. Analysis of the on/off kinetics in terms of an interaction "quasipotential" allows the positions of the C-terminal modifications to be determined with an accuracy of about three residues. Moreover, our results uncover a previously unobserved mechanism by which cytosolic proteins control β-barrel channels and thus a new regulatory function for PTMs.
David P Hoogerheide, Philip A Gurnev, Tatiana K Rostovtseva, Sergey M Bezrukov

2506 related Products with: Effect of a post-translational modification mimic on protein translocation through a nanopore.

50 UG100ug100ug 100ul100ug Lyophilized1 Set100ug1ml1 Set100ug Lyophilized100 ml

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#32387391   2020/05/05 To Up

Fumonisin-(Fusarium verticillioides)-contaminated feed causes hepatic oxidative stress and negatively affects broiler performance in the early stage: Does supplementation with açai flour residues (Euterpe oleracea) minimize these problems?

Fusarium verticillioides is often responsible for contamination of poultry feed with the mycotoxin fumonisin. The aim of this study was to determine whether oxidative stress caused by intake of fumonisin-contaminated feed affects broiler performance at an early stage of development, as well as to test whether the addition of açai residue flour to contaminated feed would minimize these negative effects of redox metabolism. Birds were divided into four groups, with four repetitions of five animals each: control (TC) - birds that received basal feed; TCA treatment - basal feed supplemented with 2% açai flour; TF treatment - feed experimentally contaminated with fumonisin (10 ppm); TFA treatment - fumonisin-contaminated feed (10 ppm) and supplemented with açai fluor (2%). The experiment lasted 20 days, that is, the first 20 days of the chicks' lives. At the end of the experiment, the birds were weighed, and blood, intestine and liver samples were collected. The TCA and TFA had greater body weights and weight gain than did TF. Further, TCA and TFA had lower feed conversion than did TF. Açai flour intake (TCA and TFA) stimulated albumin synthesis and reduced serum AST activity. Nitrate/nitrite (NOx) levels were higher in serum of fumonisin-challenged (TF) birds than in groups; NOx levels were also higher in the livers of all test groups (TF, TCA and TFA) than in TC. Serum glutathione S-transferase (GST) activity was lower in fumonisin-consuming groups (TF and TFA); this was different from what occurred in the liver, that is, higher GST activity in TF and lower activity in TFA than in TC. Catalase activity (CAT) was also higher in the fumonisin-challenged groups (TF and TFA) and the groups supplemented with açai flour (TCA) than in TC. Serum reactive species (RS) and TBARS (lipid peroxidation) levels in the liver were lower in birds supplemented with açai flour and exposed to fumonisin. These data suggest that the addition of açai flour in the feed of early chickens improves animal performance and minimizes the effects of hepatic oxidative stress in birds fed fumonisin-contaminated feed.
Marcela C S Sousa, Gabriela M Galli, Nathieli B Bottari, Davi F Alba, Karoline W Leal, Thalison F Lopes, Letícia Druzian, Maria Rosa C Schetinger, Eduardo M Gloria, Ricardo E Mendes, Lenita M Stefani, Aleksandro S Da Silva

1769 related Products with: Fumonisin-(Fusarium verticillioides)-contaminated feed causes hepatic oxidative stress and negatively affects broiler performance in the early stage: Does supplementation with açai flour residues (Euterpe oleracea) minimize these problems?

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