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The aim of this review article is to introduce the reader to the state-of-the-art of the contribution that proteomics and metabolomics sciences are currently providing for cystic fibrosis (CF) research: from the understanding of cystic fibrosis transmembrane conductance regulator (CFTR) biology to biomarker discovery for CF diagnosis. Our work particularly focuses on CFTR post-translational modifications and their role in cellular trafficking as well as on studies that allowed the identification of CFTR molecular interactors. We also show how metabolomics is currently helping biomarker discovery in CF. The most recent advances in these fields are covered by this review, as well as some considerations on possible future scenarios for new applications.

The formation of the biomolecular corona represents a crucial factor in controlling the biological interactions and trafficking of nanomaterials. In this context, the availability of key epitopes exposed on the surface of the corona, and able to engage the biological machinery, is important to define the biological fate of the material. While the full biomolecular corona composition can be investigated by conventional bottom-up proteomics, the assessment of the spatial orientation of proteins in the corona in a high-throughput fashion is still challenging. In this work, we show that labeling corona proteins with isobaric tags in their native conditions and analyzing the MS/MS spectra of tryptic peptides allow an easy and high-throughput assessment of the inner/outer orientation of the corresponding proteins in the original corona. We put our results in the context of what is currently known of the protein corona of graphene-based nanomaterials. Our conclusions are in line with previous data and were confirmed by in silico calculations.

Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. Different mutations involving the cystic fibrosis transmembrane regulator protein (CFTR) gene, which encodes the CFTR channel, are involved in CF. A number of life-prolonging therapies have been conceived and deeply investigated to combat this disease. Among them, the administration of the so-called CFTR modulators, such as correctors and potentiators, have led to quite beneficial effects. Recently, based on QSAR (quantitative structure activity relationship) studies, we reported the rational design and synthesis of compound 2, an aminoarylthiazole-VX-809 hybrid derivative exhibiting promising F508del-CFTR corrector ability. Herein, we explored the docking mode of the prototype VX-809 as well as of the aforementioned correctors in order to derive useful guidelines for the rational design of further analogues. In addition, we refined our previous QSAR analysis taking into account our first series of in-house hybrids. This allowed us to optimize the QSAR model based on the chemical structure and the potency profile of hybrids as F508del-CFTR correctors, identifying novel molecular descriptors explaining the SAR of the dataset. This study is expected to speed up the discovery process of novel potent CFTR modulators.

Malva sylvestris (MS) is a medicinal herb known worldwide for its beneficial effects due to the several active molecules present in its leaves and flowers. These compounds have shown antioxidant and anti-inflammatory properties and thus can be helpful in treatments of burns and chronic wounds, characterized mainly by high levels of free radicals and impairments of the inflammatory response. In this work, we propose bilayer films as wound dressings, based on poly(vinylpyrrolidone) (PVP) and sodium alginate loaded with M. sylvestris extracts from leaves and flowers and fabricated by combining solvent-casting and rod-coating methods. The top layer is produced in two different PVP/alginate ratios and loaded with the MS flowers’ extract, while the bottom layer is composed of PVP and MS leaves’ extract. The bilayers were characterized morphologically, chemically, and mechanically, while they showed superior self-adhesive properties on human skin compared to a commercial skin patch. The materials showed antioxidant activity, release of the bioactive compounds, and water uptake property. Moreover, the anthocyanin content of the flower extract provided the films with the ability to change color when immersed in buffers of different pH levels. In vitro tests using primary keratinocytes demonstrated the biocompatibility of the MS bilayer materials and their capacity to enhance the proliferation of the cells in a wound scratch model. Finally, the best performing MS bilayer sample with a PVP/alginate ratio of 70:30 was evaluated in mice models, showing suitable resorption properties and the capacity to reduce the level of inflammatory mediators in UVB-induced burns when applied to an open wound. These outcomes suggest that the fabricated bilayer films loaded with M. sylvestris extracts are promising formulations as active and multifunctional dressings for treating skin disorders.

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