Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.     

Activity of Riminophenazines against Mycobacterium tuberculosis: A Review of Studies that Might be Contenders for Use as Antituberculosis Agents

Tuberculosis is one of the leading cause of death in the world, mainly due to the increasing number of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. Factors such as the HIV pandemic contribute further. Also, the ineffectiveness of the chemotherapy in current use increases the mortality rate. Therefore, new and repurposed antituberculosis drugs are urgently needed for the treatment of MDR-TB, and riminophenazines are among those drugs that are being reinvestigated for their potential in the treatment of TB. This review delivers a brief historical account of riminophenazines, their general synthesis, mechanisms of action, and their physicochemical properties. The discussion is limited to those studies that investigated the activity of these compounds as antituberculosis agents. Given their unique properties, this review will be of great significance in giving direction towards the design and development of new riminophenazine analogues.     

Capture‐Tag‐Release: A Strategy for Small Molecule Labeling of Native Enzymes

A strategy for labeling native enzymes in a manner that preserves their activity is reported: capture–tag–release (CTR). Key to this approach is the small molecule CTR probe that contains an enzyme inhibitor, benzophenone crosslinker, and aryl phosphine ester. After UV‐derived capture of the enzyme, addition of an azide‐containing tag triggers a Staudinger ligation that labels the enzyme. A further consequence of the Staudinger ligation is fragmentation of the CTR probe, thus releasing the inhibitor and restoring enzymatic activity. As a proof‐of‐principle, the CTR strategy was applied to the hydrolase β‐galactosidase. The enzyme was efficiently labeled with biotin, and the kinetic data for the biotinylated enzyme were comparable to those for unlabeled β‐galactosidase. The CTR probe exhibits excellent targeting specificity, as it selectively labeled β‐galactosidase in a complex protein mixture.     

Inhibition of Hydroperoxy-, Keto- and Hydroxy-FAME by Alpha- and Delta-Tocopherol at Rancimat Conditions

The effects of α‐ and δ‐tocopherol on inhibition of hydroperoxides, keto and hydroxy compounds under Rancimat conditions, i.e. 100 °C and air bubbling, were studied in samples of fatty acid methyl esters (FAME) obtained from high linoleic (HL) and high oleic (HO) sunflower oils. Primary hydroperoxides from methyl linoleate and methyl oleate and secondary keto and hydroxy compounds derived from methyl linoleate hydroperoxides were analyzed by HPLC–UV‐ELS. Different tocopherol concentrations, namely, 10, 50, 100, 500 and 1000 mg/kg, were tested. Irrespective of the lipid substrate and the initial concentration of tocopherol, results showed that the content of hydroperoxides accumulated during the induction period was remarkably higher in the samples containing δ‐tocopherol. The relative concentrations of oleate hydroperoxides in the HO samples were also higher in the presence of δ‐tocopherol. α‐Tocopherol was more effective in inhibiting hydroperoxides at low levels, with 100 mg/kg as optimal concentration, while δ‐tocopherol displayed optimal protection at 1000 mg/kg. Under the oxidation conditions applied, neither α‐ nor δ‐tocopherol showed a protective effect on hydroperoxide decomposition at any level assayed. Formation of keto‐ and hydroxy‐dienes was more related to the concentration of their hydroperoxide precursors. Furthermore, both tocopherols gave rise to increased concentrations of ketodienes at 500 and 1000 mg/kg compared to the controls. Such an effect was more pronounced for α‐tocopherol and in the HL samples.     

Mechanical characteristics of porous hydroxyapatite/oxide composites produced by post-sintering hot isostatic pressing

Porous hydroxyapatite and hydroxyapatite/oxide composites, with 10 wt% addition of Y₂O₃, ZrO₂ or TiO₂ have been prepared by hot isostatic pressing after pressureless sintering, and their phase composition, mechanical properties and microstructure investigated. The quantitative X-ray diffraction analyses reveal that the addition of Y₂O₃ inhibits the hydroxyapatite decomposition completely during the consolidation processes as a result of the Y ion dissolution into the hydroxyapatite lattice. On the contrary, it is found that the addition of ZrO₂ or TiO₂ enhances the decomposition of hydroxyapatite into Ca₃(PO₄)₂, which causes the transformation of the starting oxides. The mechanical characterization of the materials has been accomplished by three-point flexure tests, and nanoindentation and microhardness measurements. Post-sintering hot isostatic pressed pure hydroxyapatite, which resulted in a porous biphasic material with 13.2 wt% β-Ca₃(PO₄)₂, exhibited the best mechanical properties. The failure of hydroxyapatite-10Y₂O₃ during the flexure tests was no catastrophic in contrast to the catastrophic behaviour found in the other materials.     

Identification of the origin of commercial enological tannins by the analysis of monosaccharides and polyalcohols

The monosaccharide and polyalcohol composition of 28-samples of different commercial tannins, including oak wood, grape seed and skin, plant gall, chestnut, quebracho and gambier, has been evaluated by gas chromatography–mass spectrometry after derivatization into their trimethylsilyl ethers. Quercitol was found to be characteristic of oak tannins, whereas gall plant tannins could be differentiated by their content of pinitol. Myo-inositol and arabitol were detected in tannins from quebracho. These polyalcohols, together with muco-inositol and chiro-inositol, were found in tannins from chestnut while bornesitol was found to be characteristic of tannins from gambier. Monosaccharide composition also helped to distinguish among tannin origins: arabinose, xylose, fructose and glucose were quantified in oak, quebracho and chestnut tannins, whereas only fructose and glucose were detected in plant gall and grape tannins. These results imply that the qualitative study of monosaccharides and polyalcohols could help to determine and control the authenticity of enological tannins.     

DETERMINATION OF β-GLUCAN IN WORT AND BEER BY ITS BINDING WITH CALCOFLUOR,USING A FLUORIMETRIC FLOW-INJECTION-ANALYSIS (FIA) METHOD

The FIA-fluorimetric methods for the determination of β-glucan in worts and beers have been investigated, modified and improved. Fluorescence is excited by using a mercury lamp and a 338 nm band-pass excitation filter, and detected using a 425 nm long-pass emission filter. It has been found that an increase of the ionic strength of the eluent, up to a maxium of 1% Sodium Chloride, increases the range of β-glucan molecular weights effectively bound by Calcofluor. The influence of the low molecular weight components of wort and beer: dextrins, aminoacids, etc, has been studied and found that their effect is negligible. The interference of wort and beer colour on the measurement of β-glucan has been quantified and several approaches are given to overcome it. Thirty-six European beers have been analyzed for β-glucan content. The possible detection of the addition of exogenous β-glucanases to wort and beer is discussed.     

Disconnecting outcomes and evaluations: The role of negotiator focus.

Three experiments explored the role of negotiator focus in disconnecting negotiated outcomes and evaluations. Negotiators who focused on their target prices, the ideal outcome they could obtain, achieved objectively superior outcomes compared with negotiators who focused on their lower bound (e.g., reservation price). Those negotiators who focused on their targets, however, were less satisfied with their objectively superior outcomes. In the final experiment, when negotiators were reminded of their lower bound after the negotiation, the satisfaction of those negotiators who had focused on their target prices was increased, with outcomes and evaluations becoming connected rather than disconnected. The possible negative effects of setting high goals and the temporal dimensions of the disconnection and reconnection between outcomes and evaluations are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)