Role of nanostructured aggregation of chitosan derivatives on [5-methionine]enkephalin affinity

Affinities of quaternary ammonium-chitosan conjugates, their thiolated derivatives and corresponding nanostructured aggregates towards the hydrophilic drug [5-methionine]enkephalin were compared by Nuclear Magnetic Resonance (NMR) spectroscopic methods based on proton selective relaxation rate measurements. Nanoaggregates showed enhanced drug affinity in comparison with corresponding polymers, especially in the case of thiolated systems

MiR200 and MiR302: Two big families influencing stem cell behavior

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-\uce\ub2, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-\uce\ub2 plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-\uce\ub2 activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate

Efficient Ligand Passivation Enables Ultrastable CsPbX3 Perovskite Nanocrystals in Fully Alcohol Environments

Halide perovskite nanocrystals (PNCs) have demonstrated their wide potential to fabricate efficient optoelectronic devices and to prepare promising photocatalysts for solar-driven photo(electro)chemical reactions. However, their use in most of the practical applications is limited due to the instability of PNCs in polar environments. Here, the preparation of non-encapsulated CsPbX3 nanocrystals dispersed in fully alcohol environments, with outstanding stability through surface defect passivation strategy is reported. By using didodecyldimethylammonium bromide (DDAB) during material post-treatment, highly luminescent CsPbBr3 PNCs with remarkable stability in methanol/butanol medium up to 7 months with near-unity photoluminescence quantum yield are achieved. This approach is extrapolated to stabilize iodine-based CsPbBr3-xIx and CsPbI3 PNCs, showing an improvement of their photoluminescence features and stability in these high polar alcohols up to 6 h. DDAB mediates the defect suppression through ligand exchange and avoids the full permeation of alcohol to be in contact with the PNCs. In this context, DDAB induces ionization of alcohol molecules to strengthen the surface passivation. The findings open the door to the development of long-term stable CsPbX3 PNCs with high optical performance to be used in polar environments.This work was supported by the European Innovation Council (EIC) via OHPERA project (grant agreement 101071010), the Spanish Ministry of Science and Innovation under projects STABLE (PID2019-107314RB-I00) and ECOCAT (PID2020-116093RB-C41), the Spanish Ministry of Science and Innovation under project She-LED (PID2021-122960OA-I00), and the Generalitat Valenciana via Prometeo Grant Q-Solutions (CIPROM/2021/078). C.A.M. acknowledges APOSTD grant (APOSTD/2021/251) for funding. The authors also thank the Ministry of Education, Youth and Sports of the Czech Republic for the financial support of XPS measurements using CEMNAT infrastructure (project LM 2018103). The authors are very grateful to the “Serveis Centrals d'Instrumentació Científica (SCIC)” of the Universitat Jaume I

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

Melatonin and Vitamin D Orchestrate Adipose Derived Stem Cell Fate by Modulating Epigenetic Regulatory Genes

Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2. Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype

Chiral mono- and dicarbamates derived from ethyl (S)-lactate: convenient chiral solvating agents for the direct and efficient enantiodiscrimination of amino acid derivatives by 1H NMR spectroscopy

New lactate-based CSAs for 1H NMR enantiodifferentiation of amino acid derivatives

Chiral NMR solvating additives for differentiation of enantiomers

This chapter will describe the general features and main categories of chiral solvating agents (CSAs) for NMR spectroscopy, spanning from low-medium sized CSAs to macrocyclic ones. CSAs based on chiral ionic liquids will be introduced, in view of their increasing popularity, and, finally, a short paragraph will be dedicated to special applications of CSAs in particular experimental conditions. Several valuable works, which are mainly devoted to investigate enantiodifferentiation mechanisms by NMR, will not be discussed The main objective is to identify the current trend in the research areas dedicated to the development of new CSAs for NMR spectroscopy

Postfazione. le parole delle parentele: dal tradurre al fare

In Making Kin. Fare parentele non popolazioni l’invito condi- viso a fare giustizia multispecie contro ogni sfruttamento suprematista emerge da sette tastiere differenti, e dunque da sette differenti posizionamenti personali e politici. Clar- ke, Haraway, Benjamin, Murphy, TallBear, Yu-Ling Huang e Chia-Ling Wu insieme, ma con argomentazioni e collocazio- ni diverse, sostengono che ai tempi del Capitalocene occorre ripensare la riproduzione della specie sapiens in relazione alla rigenerazione della Terra tutta, allo scopo di favorire il diffondersi di parentele transpecie, degeneri, crossrazziali

USING 1H-NMR TO STUDY A NANOPARTICULATE SYSTEM FOR DEXAMETHASONE PHOSPHATE RELEASE AND MUCOADHESIVITY

Purpose: Preparing mucoadhesive nanoparticles (NP) based on quaternary ammonium-chitosan conjugates or their thiolated derivatives, medicated with dexamethasone phosphate (DXP), and studying DXP release from NP and NP mucoadhesivity by a non-invasive 1H-NMR method. Methods: Two structurally different quaternary ammonium-chitosan conjugates, synthesised at 60 °C (N+-Ch(60°)) and 50°C (N+-Ch(50°)), respectively, and their thiolated derivatives (N+-Ch(60°)-SH and N+-Ch(50°)-SH, respectively) were used to prepare DXP medicated NP by ionotropic gelation with hyaluronic acid (HA). Drug release from NP was studied by quantitative NMR (600 MHz, D2O, 25 °C) analyses in the presence or absence of mucin. Translational diffusion coefficients of DXP were measured by Diffusion Ordered SpectroscopY (DOSY) in the presence of each polymer, or mucin, or NP, or NP/mucin or polymer/mucin mixtures. Results: NP were in the 300-400 nm size range. The encapsulation efficiency was in the 20-30% range. DXP was retained for prolonged times by all NP types. Drug release was favoured by the presence of mucin, pointing to NP mucoadhesivity. All NP constituent polymers showed a remarkable affinity for the drug, consistent with the NP drug-retaining ability. Conclusion: An efficient NMR spectroscopic protocol has been developed for measuring drug release from NP and detecting NP mucoadhesivity. The prolonged drug retention within NP suggests that the expected NP internalization by cells of mucous epithelia could create a drug reservoir within the epithelium for a prolonged drug activity