Biophysical and Biological Tools to Better Characterize the Stability,Safety and Efficacy of a Cosmeceutical for Acne-Prone Skin

(1) Background: Acne is a widespread skin disease, especially among adolescents. Following the COVID-19 pandemic and the use of masks, the problem has been affecting a greater number of people, and the attention of the skin care beauty routine cosmetics has been focused on the “Maskne”, caused by the sebum excretion rate (SER) that stimulates microbial proliferation. (2) Methods: the present study was focused on the rheological characterization and quality assurance of the preservative system of an anti-acne serum. The biological effectiveness (cytotoxicity—skin and eye irritation—antimicrobial, biofilm eradication and anti-inflammatory activity) was evaluated in a monolayer cell line of keratinocytes (HaCaT) and on 3D models (reconstructed human epidermis, RHE and human reconstructed corneal epithelium, HCE). The Cutibacterium acnes, as the most relevant acne-inducing bacterium, is chosen as a pro-inflammatory stimulus and to evaluate the antimicrobial activity of the serum. (3) Results and Conclusions: Rheology allows to simulate serum behavior at rest, extrusion and application, so the serum could be defined as having a solid-like behavior and being pseudoplastic. The preservative system is in compliance with the criteria of the reference standard. Biological effectiveness evaluation shows non-cytotoxic and irritant behavior with a good antimicrobial and anti-inflammatory activity of the formulation, supporting the effectiveness of the serum for acne-prone skin treatment.     

Complementary Approaches to Imaging Subcellular Lipid Architectures in Live Bacteria Using Phosphorescent Iridium Complexes and Raman Spectroscopy

A family of three neutral iridium(III) tetrazolato complexes are investigated as bacterial imaging agents. The complexes offer a facile tuning of the emission colour from green (520 nm) to red (600 nm) in aqueous media, while keeping the excitation wavelength unchanged. The three complexes do not inhibit the bacterial growth of Bacillus Cereus, used as a model in this study, and exhibit extremely fast cellular uptake. After a minute incubation time, the nontoxic complexes show subcellular localisation in spherical structures identified as lipid vacuoles. Confocal Raman imaging has been exploited for the first time on live bacteria, to provide direct and label-free mapping of the lipid-enriched organelles within B. cereus, complementing the use of luminescent probes. Examination of the Raman spectra not only confirmed the presence of lipophilic inclusions in B. cereus but offered additional information about their chemical composition, suggesting that the lipid vacuoles may contain polyhydroxybutyrate (PHB).     

Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction: an in silico study

Journal of Computer-Aided Molecular Design - Some of the main challenges faced in drug discovery are pocket flexibility and binding mode prediction. In this work, we explored the aromatic cage...     

Deuterium-depleted water: A new tracer to label pulmonary surfactant lipids in adult rabbits

Stable isotope tracing can be safely used for metabolic studies in animals and humans. The endogenous biosynthesis of lipids (lipogenesis) is a key process throughout the entire life but especially during brain and lung growth. Adequate synthesis of pulmonary surfactant lipids is indispensable for life. With this study, we report the use of deuterium-depleted water (DDW), suitable for human consumption, as metabolic precursor for lipogenesis. We studied 13 adult rabbits for 5 days. Four rabbits drank tap water (TW) and served as controls; in four animals, DDW was substituted to drinking water, whereas five drank deuterium-enriched water (DEW). After 5 days, a blood sample and a bronchoalveolar lavage (BAL) sample were collected. The ²H/¹H (δ²H) of BAL palmitic acid (PA) desaturated phosphatidylcholine (DSPC), the major phospholipid of pulmonary surfactant, and of plasma water was determined by high-resolution mass spectrometry. We found that the δ²H values of DDW, DEW and TW were −984 ± 2‰, +757 ± 2‰ and −58 ± 1‰, respectively. After 5 days, plasma water values were −467 ± 87‰, +377 ± 56‰ and −53 ± 6‰, and BAL DSPC-PA was −401 ± 27‰, −96 ± 38‰ and −249 ± 9‰ in the DDW, DEW and TW, respectively. With this preliminary study, we demonstrated the feasibility of using DDW to label pulmonary surfactant lipids. This novel approach can be used in animals and in humans, and we speculate that it could be associated with more favourable study compliance than DEW in human studies.     

Complex ball quotients from manifolds of K3[n]-type

We describe periods of irreducible holomorphic symplectic manifolds of $K{3}^{[n]}$-type with a non-symplectic automorphism of prime order $p\ge 3$. These turn out to lie on complex ball quotients and we are able to give a precise characterization of when the period map is bijective by introducing the notion of $K(T)$-generality.     

Bacteria‐Resistant Single Chain Cyclized/Knotted Polymer Coatings

Further to conventional linear, branched, crosslinked, and dendritic polymers, single chain cyclized/knotted polymers (SCKPs) have emerged as a new class of polymer structure with unique properties. Herein, the development of bacteria‐resistant SCKPs is reported and the effect of this structure on the resistance of polymer materials to bacteria is investigated. Four SCKPs were synthesized by reversible addition fragmentation chain transfer (RAFT) homopolymerization of multivinyl monomers (MVMs) and then crosslinked by UV light to form SCKP films. Regardless of MVM type used, the resulting SCKP films showed much higher resistance to bacteria, and up to 75 % less bacterial attachment and biofilm formation, in comparison with the corresponding non‐SCKP films. This is due to the altered surface morphology and hydrophobicity of the SCKP films. These results highlight the critical role of the SCKP structure in enhancing the resistance of polymeric materials to bacteria.     

Identification of Protein Functional Regions

Protein sequence stores the information relative to both functionality and stability, thus making it difficult to disentangle the two contributions. However, the identification of critical residues for function and stability has important implications for the mapping of the proteome interactions, as well as for many pharmaceutical applications, e. g. the identification of ligand binding regions for targeted pharmaceutical protein design. In this work, we propose a computational method to identify critical residues for protein functionality and stability and to further categorise them in strictly functional, structural and intermediate. We evaluate single site conservation and use Direct Coupling Analysis (DCA) to identify co-evolved residues both in natural and artificial evolution processes. We reproduce artificial evolution using protein design and base our approach on the hypothesis that artificial evolution in the absence of any functional constraint would exclusively lead to site conservation and co-evolution events of the structural type. Conversely, natural evolution intrinsically embeds both functional and structural information. By comparing the lists of conserved and co-evolved residues, outcomes of the analysis on natural and artificial evolution, we identify the functional residues without the need of any a priori knowledge of the biological role of the analysed protein.