Graphene oxide accelerates TGFß-mediated epithelial-mesenchymal transition and stimulates pro-inflammatory immune response in amniotic epithelial cells.

The application of biomaterials on immune regenerative strategies to deal with unsolved pathologies is getting attention in the field of tissue engineering. In this context, graphene oxide (GO) has been proposed as an immune-mimetic material largely used for developing stem cell-based regenerative therapies, since it has shown to influence stem cell behavior and modulate their immune response. Similarly, amniotic epithelial stem cells (AECs) are getting an increasing clinical interest as source of stem cells due to their great plasticity and immunomodulatory paracrine activities, even though GO bio-mimetic effects still remain unknown. To this aim, GO-functionalized glass coverslips have been used for AECs culture. The results demonstrated how GO-coating is able to induce and accelerate the Epithelial-Mesenchymal Transition (EMT), in a process mediated by the intracellular activation of TGFß1-SMAD2/3 signaling pathway. The trans-differentiation towards mesenchymal phenotype provides AECs of migratory ability and substantially changes the pattern of cytokines secretion upon inflammatory stimulus. Indeed, GO-exposed AECs enhance their pro-inflammatory interleukins production thus inducing a more efficient activation of macrophages and, at the same time, by slightly reducing their inhibitory action on peripheral blood mononuclear cells proliferation. Therefore, the adhesion of AECs on GO-functionalized surfaces might contribute to the generation of a tailored microenvironment useful to face both the phases of the inflammation, thereby fostering the regenerative process.

Expanding natural transformation to improve beneficial lactic acid bacteria.

Nowadays, the growing human population exacerbates the need for sustainable resources. Inspiration and achievements in nutrient production or human/animal health might emanate from microorganisms and their adaptive strategies. Here, we exemplify the benefits of lactic acid bacteria (LAB) for numerous biotechnological applications and showcase their natural transformability as a fast and robust method to hereditarily influence their phenotype/traits in fundamental and applied research contexts. We described the biogenesis of the transformation machinery and we analyzed the genome of hundreds of LAB strains exploitable for human needs to predict their transformation capabilities. Finally, we provide a stepwise rational path to stimulate and optimize natural transformation with standard and synthetic biology techniques. A comprehensive understanding of the molecular mechanisms driving natural transformation will facilitate and accelerate the improvement of bacteria with properties that serve broad societal interests.

Binary control of enzymatic cleavage of DNA origami by structural antideterminants.

Controlling DNA nanostructure interaction with protein is essential in developing nanodevices with programmable function, reactivity, and stability for biological and medical applications. Here, we show that the sequence-specific action of restriction endonucleases towards sharp triangular or rectangular DNA origami exhibits a novel, binary 'on/off' behaviour, as canonical recognition sites are either essentially fully reactive, or strongly resistant to enzymatic cutting. Moreover, introduction of structural defects in the sharp triangle can activate an otherwise unreactive site, with a site-to-defect distance of ∼50 nm. We argue that site reactivity is dependent upon programmable, mechanical coupling in the two-dimensional DNA origami, with specific structural elements, including DNA nicks and branches proximal to the sites that can function as negative(anti) determinants of reactivity. Empirically modelling the constraints to DNA degrees of freedom associated with each recognition site in the sharp triangle can rationalize the pattern of suppressed reactivity towards nine restriction endonucleases, in substantial agreement with the experimental results. These results provide a basis for a predictive understanding of structure-reactivity correlates of specific DNA nanostructures, which will allow a better understanding of the behaviour of nucleic acids under nanoscale confinement, as well as in the rational design of functional nanodevices based on self-assembling nucleic acids.