Chitosan–Quercetin Bioconjugate as Multi‐Functional Component of Antioxidants and Dual‐Responsive Hydrogel Networks

Multifunctional hydrogels based on chitosan–quercetin (CHITQ) conjugate are prepared by a thermo‐induced radical procedure in the presence of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and N,N′‐methylenebis(acrylamide) (MEBA). At first, quercetin (Q) is grafted onto chitosan backbone with a functionalization degree of 275 mg of Q per gram of conjugate, as calculated by ¹H‐NMR analyses to impart antioxidant properties to the polysaccharide. Then, a pH and temperature sensitive hydrogel was obtained by involving CHITQ and NIPAAm in the polymerization reaction. The accessibility of phenolic moieties is modified in response to the hydrogel swelling/deswelling, as confirmed by antioxidant tests performed at different temperatures. Dual stimuli‐responsive hydrogels are proposed for the delivery of caffeine as model drug. The release profiles of caffeine depict a system particularly performing as on/off device at acidic pH with excellent applicability prospects.     

Evaluation of the tablet core factors influencing the release kinetics and the loadability of push-pull osmotic systems

Push-pull osmotic systems have been developed to deliver poorly soluble drugs in a modified-release fashion. The aim of this study was to investigate the influence of the tablet core factors on the drug release kinetics and loadability. The release kinetics was efficiently modulated by varying either the proportion of osmotic agent or the drug layer polymer grade as an alternative to change the membrane characteristics. High osmotic agent proportions and viscous-grade polymers were recommended to formulate high drug loads up to 20% without losing both the release completeness and the zero-order drug release kinetics.     

Involvement of Ligninlike Compounds in Toxicity of Dietary Alder Leaf Litter Against Mosquito Larvae

The toxicological characteristics of dietary decomposed alder leaf litter against mosquito larvae were further investigated through enzymatic and chemical purification of a phenoliclike cell-wall fraction isolated from crude litter. The toxicity of the subfractions obtained was controlled by standard bioassays on third instars of Aedes aegypti chosen as a reference target species. Enzymatic hydrolyses of the cell-wall fraction were performed with caylase, pectolyase, esterase, and -glycosidase, in order to release, respectively, cellulose material and phenolic compounds bound to lignins. These treatments did not affect the larvicidal activity and the phenolic activity of the cell-wall fraction. Chemical alkaline and acid hydrolyses were carried out to break ester and glycosidic bonds of the cell-wall fraction. Comparison of HPLC profiles of the hydrolysates from both toxic and nontoxic fractions did not reveal differences between the phenolic acids released. Aluminum chloride, known for its phenolic complexing activity, counteracted the larvicidal activity of the cell-wall fraction. Altogether, these results suggest the involvement of ligninlike compounds in the toxicity of dietary alder leaf litter against larval mosquitoes. The toxicity of this fraction, which was very sensitive to drastic and smooth oxidations, seemed to be associated with a strong oxidative potential. These results are discussed in relation to a possible mode of action of lignins in the plant–mosquito interactions.     

Determination of illicit and/or abused drugs and compounds of forensic interest in biosamples by capillary electrophoretic/electrokinetic methods

The application of capillary electrophoresis (CE) methods in forensic toxicology for the determination of illicit and/or misused drugs in biological samples is reviewed in the present paper. Sample pretreatments and direct injection modes used in CE for analysis of drugs in biological fluids are briefly described. Besides, applications of separation methods based on capillary zone electrophoresis or micellar electrokinetic chromatography with UV absorbance detection to (i) analysis of drugs of abuse, (ii) analysis of other drugs and toxicants of potential forensic interest and (iii) for metabolism studies are reviewed. Also, alternative CE methods are briefly discussed, including capillary isotachophoresis and separation on mixed polymer networks. High sensitivity detection methods used for forensic drug analysis in biological samples are then presented, particularly those based on laser induced fluorescence. A glimpse of the first examples of application of CE-mass spectrometry in forensic toxicology is finally given.     

Effect of cooking on the total antioxidant capacity and phenolic profile of some whole‐meal African cereals

BACKGROUND: At present, sorghum, fonio and millet are not placed as important commodities in the North American and European food basket, but their importance as ingredients in multigrain and gluten‐free cereal products is highlighted. Therefore in this study the phenolic profile (evaluated by liquid chromatography/tandem mass spectrometry), total phenolic content (assessed by Folin–Ciocalteu assay) and total antioxidant capacity were measured in three African whole grains, i.e. sorghum (Sorghum bicolor ssp. bicolor), fonio (Digitaria exilis) and pearl millet (Pennisetum glaucum L.), before and after a cooking procedure. RESULTS: After the cooking process, soluble phenolic acids increased significantly in sorghum, whereas bound ones and anthocyanins decreased significantly. In millet the cooking process significantly enhanced soluble phenolic acids without affecting those bound, whereas in fonio a slight but significant decrease in almost all soluble phenolic acids was observed along with a significant increase in bound ones. Finally, the cooking process negatively affected both total phenolic content and total antioxidant capacity. CONCLUSION: This is one of the few reports dealing with the antioxidant compounds of these three African whole grains in which the effect of cooking was also evaluated. The data suggested that, to improve their antioxidant properties, specific cultivars should be selected and the cooking procedures carefully considered. Copyright © 2012 Society of Chemical Industry     

Modulation of the biological activity of microRNA-210 with peptide nucleic acids (PNAs)

Herein we describe the activity of a peptide nucleic acid (PNA) that targets microRNA‐210 (miR‐210), which is associated with hypoxia and is modulated during erythroid differentiation. PNAs directed against miR‐210 were designed to bind with high affinity to the target RNA strand and to undergo efficient uptake in target cells. A polyarginine–PNA conjugate directed against miR‐210 (Rpep‐PNA‐a210) showed both very high affinity for RNA and efficient uptake into target cells without the need for transfection reagents. An unmodified PNA of the same sequence displayed the ability to bind RNA, but cellular uptake was very poor. Consistent with this, only Rpep‐PNA‐a210 strongly inhibited miR‐210 activity, as evaluated by assays on undifferentiated K562 cells and on cells treated with mithramycin, which was found to induce erythroid differentiation and miR‐210 overexpression. Targeting miR‐210 by Rpep‐PNA‐a210 resulted in: 1) a decrease in miR‐210 levels as measured by RT‐PCR, 2) up‐regulation of raptor mRNA, 3) a decrease in γ‐globin mRNA, and 4) decreased expression of differentiated functions (i.e., proportion of benzidine‐positive cells, content of embryo‐fetal hemoglobins). The efficient delivery of anti‐miR PNAs through a suitable peptide carrier (Rpep‐PNA‐a210) leads to the inhibition of miR‐210 activity, altering the expression of miR‐210‐regulated erythroid functions.     

Classification of Carnot Algebras: the Semi-Rigid Cases

A Carnot algebra is a graded nilpotent Lie algebra L = L ₁⊕⋯⊕L _r generated by L ₁. The bidimension of the Carnot algebra L is the pair (dim L ₁, dim L). A Carnot algebra is said to be rigid if it is isomorphic to any of its small perturbations in the space of Carnot algebras of the prescribed bidimension, while it is said to be semi-rigid if it admits only a finite number of deformations: any small perturbation gives a finite number of nonisomorphic rigid Carnot algebras. A complete classification of rigid Carnot algebras was given in a previous work [2]. In this paper, we concentrate on the classification of semi-rigid cases and their normal form.      

Synchrotron X-ray computed microtomography investigation of a mortar affected by alkali–silica reaction: a quantitative characterization of its microstructural features

Alkali–silica reaction (ASR) is one of the most important weathering processes in cement-based materials. The damages caused by ASR have been qualitatively investigated with a number of different techniques. In this study, we present a procedure to obtain quantitative morphological parameters of the ASR reaction effects using synchrotron X-ray microtomography data. We found three different kinds of voids due to the effect of three different mechanisms: (i) cracks from ASR expansion, (ii) irregular-shaped voids due to the aggregate particles dissolution, and (iii) bubbles due to the cement paste preparation. We were able to separate them using morphological parameters (such as surface/volume ratio and aspect-ratio) calculated for each object, thus obtaining, e.g., volume fractions for each kind of voids. From the orientation data, we also studied if any shape preferred orientation was present in the sample, concerning the fractures network, and we found no appreciable preferred orientation. The new analysis procedure we applied in this study proved to be an effective approach for the quantitative characterization of the effects (cracks and porosity development by aggregate weathering) of the ASR reaction in mortars.     

Cellular uptakes, biostabilities and anti-miR-210 activities of chiral arginine-PNAs in leukaemic K562 cells

A series of 18‐mer peptide nucleic acids (PNAs) targeted against micro‐RNA miR‐210 was synthesised and tested in a cellular system. Unmodified PNAs, R₈‐conjugated PNAs and modified PNAs containing eight arginine residues on the backbone, either as C2‐modified (R) or C5‐modified (S) monomers, all with the same sequence, were compared. Two different models were used for the modified PNAs: one with alternated chiral and achiral monomers and one with a stretch of chiral monomers at the N terminus. The melting temperatures of these derivatives were found to be extremely high and 5 M urea was used to assess differences between the different structures. FACS analysis and qRT‐PCR on K562 chronic myelogenous leukaemic cells indicated that arginine‐conjugated and backbone‐modified PNAs display good cellular uptake, with best performances for the C2‐modified series. Resistance to enzymatic degradation was found to be higher for the backbone‐modified PNAs, thus enhancing the advantage of using these derivatives rather than conjugated PNAs in the cells in serum, and this effect is magnified in the presence of peptidases such as trypsin. Inhibition of miR‐210 activity led to changes in the erythroid differentiation pathway, which were more evident in mithramycin‐treated cells. Interestingly, the anti‐miR activities differed with use of different PNAs, thus suggesting a role of the substituents not only in the cellular uptake, but also in the mechanism of miR recognition and inactivation. This is the first report relating to the use of backbone‐modified PNAs as anti‐miR agents. The results clearly indicate that backbone‐modified PNAs are good candidates for the development of very efficient drugs based on anti‐miR activity, due to their enhanced bioavailabilities, and that overall anti‐miR performance is a combination of cellular uptake and RNA binding.