Despite the relevance of carbohydrates as cues in eliciting specific biological responses, glycans have been rarely exploited in the study of neuronal physiology. We report thereby the study of the effect of neoglucosylated collagen matrices on neuroblastoma F11 cell line behavior. Morphological and functional analysis clearly showed that neoglucosylated collagen matrices were able to drive cells to differentiate. These data show for the first time that F11 cells can be driven from proliferation to differentiation without the use of chemical differentiating agents. Our work may offer to cell biologists new opportunities to study neuronal cell differentiation mechanisms in a cell environment closer to physiological conditions.
A new hydrogel, totally based on gelatin has been synthesized by cross-linking thiolated gelatin with pentenoyl gelatin, via thiol-ene click chemistry. Preliminary cytocompatibility assays with hBMSC showed good cell compatibility
3'-Sialyllactose and 6'-sialyllactose have been covalently linked to collagen films. Preliminary in vitro study on the behavior of mesenchymal stem cells (MSCs) in terms of cell viability, proliferation and induction of osteogenic and chondrogenic related genes has been performed. Results indicate that sialoside epitopes on collagen surface represent a suitable support for MSCs adhesion and cell proliferation, moreover, the neoglycosylation provide MSCs with different and specific stimuli, saccharide-type depending, in term of expression of osteogenic and chondrogenic related genes. In particular, 3'-sialyllactose significantly upregulate the expression of RUNX2 and ALP, well-known markers of osteogenesis, whereas 6'-sialyllactose up-regulate the expression of chondrocyte marker ACAN. Because no osteogenic or chondrogenic supplements in culture media were added, the inductive effect in terms of increased gene expression has to be ascribed uniquely to collagen surface functionalization. These results support the promising role of sialosides in the regulation of stem cells fate and open brilliant perspective for the future use of the presented approach toward osteochondral tissue engineering applications.
Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customised biomaterials able to mimic extracellular matrix (ECM) functionalities represents one of the major strategies to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during the regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review, new strategies and future perspectives of such synthetic cell microenvironments will be highlighted.
7-Deoxy-uniflorine A (6), synthesized ex novo with a straightforward and simple strategy, and the analogues 4, 5 and 7, were evaluated as potential inhibitors of insect trehalase from Chironomus riparius and Spodoptera littoralis. All the compounds were tested against porcine trehalase as the mammalian counterpart and α-amylase from human saliva as a relevant glucolytic enzyme. The aim of this work is the identification of the simplest pyrrolizidine structure necessary to impart selective insect trehalase inhibition, in order to identify new specific inhibitors that can be easily synthesized compared to our previous reports with the potential to act as non-toxic insecticides and/or fungicides. All the derivatives 4-7 proved to be active (from low micromolar to high nanomolar range activity) towards insect trehalases, while no activity was observed against α-amylase. In particular, the natural compound uniflorine A and its 7-deoxy analogue were found to selectively inhibit insect trehalases, as they are inactive towards the mammalian enzyme. The effect of compound 6 was also analyzed in preliminary in vivo experiments.These new findings allow the identification of natural uniflorine A and its 7-deoxy analogue as the most promising inhibitors among a series of pyrrolizidine derivatives for future development in the agrochemical field, and the investigation also outlined the importance of the stereochemistry at C-6 of pyrrolizidine nucleus to confer such enzyme specificity. IntroductionCasuarine 1 (Fig. 1) is a naturally occurring highly oxygenated pyrrolizidine alkaloid obtained from Casuarina equisetifolia. Together with its 6-α-glucopyranosyl conjugate (2), 1 which is found in C. equisetifolia and Eugenia jambolana, 2 it is a potent and specific α-glucosidase inhibitor. 3 In particular, both casuarine and its glucosyl derivative 2 were shown to be effective trehalase inhibitors. 4 Trehalases [EC 3.2.1.28] are retaining α-glucosidases in charge of the hydrolytic cleavage of trehalose (3, α-D-glucopyranosyl α-D-glucopyranoside), which is a disaccharide with several functions in different organisms such as fungi, mycobacteria, and insects. Trehalases are present in mammals and are responsible for the hydrolysis of ingested trehalose (intolerance to mushrooms is ascribed to the absence or deficit of trehalases) because this disaccharide is absent in their metabolism. The absence of trehalose in the metabolism of mammals, together with the physiological relevance of trehalose hydrolysis in insects, makes insect trehalase inhibition a relevant target for the development of selective insecticides that are potentially non-toxic to mammals. 5 Moreover, the design of trehalase inhibitors may help in the elucidation of the structure of the protein active site of the enzyme from different organisms, which are featured by the same substrate specificity but possess some degree of variability because they can be selectively inhibited, as shown by the previous data. 4,6 To date, only the X-ray structure of Escherichia coli tr...
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