Biopolymer- and Natural Fiber-Based Biomimetic Tissues to Realize Smart Cosmeceuticals and Nutraceuticals Using an Innovative Approach.

More sustainable and smart cosmeceuticals and nutraceuticals are necessary due to the ecological transition. In this study, a pullulan-based water solution containing chitin nanofibril-nano-lignin (CN-LG) complexes that encapsulate fish collagen polypeptide, allantoin and nicotinamide was electrospun onto a nonwoven substrate made of bamboo fibers to obtain a smart nanostructured bilayer system for releasing active molecules onto the skin or other body tissues. Infrared spectroscopy was used to characterize the composition of the bilayer system before and after rapid washing of the sample with distilled water and liquids mimicking physiological fluids. The viability of keratinocytes was studied as well as the antioxidant activity, protective activity towards UV light, metalloproteinase release of aged fibroblasts and the inhibitor activity against collagen degradation. Immunomodulatory tests were performed to investigate the anti-inflammatory activity of the bilayer system as well as its indirect antimicrobial activity. The results indicate that the bilayer system can be used in the production of innovative sustainable cosmeceuticals. In general, the adopted strategy can be extended to several smart treatments for fast release that can be commercialized as solid products, thus avoiding the use of preservatives and water.

Dexamethasone induces p21cip1/waf1 expression via FoxO3a independently of the Lamin A/C-HDAC2 interaction in Ataxia Telangiectasia.

Ataxia-Telangiectasia (A-T) is a very rare autosomal recessive multisystemic disorder which to date is still uncurable. The use of glucocorticoid analogs, such as dexamethasone (dex), can improve neurological symptoms in patients, but the molecular mechanism of action of these analogs remains unclear. Here, we report the effects of dex in regulating the interaction between Lamin A/C and HDAC2 in WT and A-T cells. Upon administration of dex to A-T cells, we first observed that the accumulation of HDAC2 on the CDKN1A promoter did not exert a repressive role on p21cip1/waf1 expression, and second, we established that HDAC2 accumulation was not dependent on Lamin A/C. Both of these results are contrary to previous reported outcomes in other cellular models. Furthermore, large amounts of LAP2α and FoxO3a were found to occupy the CDKN1A promoter with matched p21cip1/waf1 overexpression. Hence, in A-T cells p21 could be activated as a result of a dex-induced rearrangement of a multicomponent complex, composed of Lamin A/C, HDAC2, LAP2α, pRb, E2F1, and FoxO3a, at the CDKN1A gene promoter.

New human ATM variants are able to regain ATM functions in ataxia telangiectasia disease.

Ataxia telangiectasia is a rare neurodegenerative disease caused by biallelic mutations in the ataxia telangiectasia mutated gene. No cure is currently available for these patients but positive effects on neurologic features in AT patients have been achieved by dexamethasone administration through autologous erythrocytes (EryDex) in phase II and phase III clinical trials, leading us to explore the molecular mechanisms behind the drug action. During these investigations, new ATM variants, which originated from alternative splicing of ATM messenger, were discovered, and detected in vivo in the blood of AT patients treated with EryDex. Some of the new ATM variants, alongside an in silico designed one, were characterized and examined in AT fibroblast cell lines. ATM variants were capable of rescuing ATM activity in AT cells, particularly in the nuclear role of DNA DSBs recognition and repair, and in the cytoplasmic role of modulating autophagy, antioxidant capacity and mitochondria functionality, all of the features that are compromised in AT but essential for neuron survival. These outcomes are triggered by the kinase and further functional domains of the tested ATM variants, that are useful for restoring cellular functionality. The in silico designed ATM variant eliciting most of the functionality recover may be exploited in gene therapy or gene delivery for the treatment of AT patients.

Biofunctional Textiles for Aging Skin.

The skin is the largest organ in the human body, acting as the first protective barrier against the external environment aggression, such as UV rays and atmospheric nanoparticulate pollutants. On the one hand, the skin employs different antioxidant agents to protect its natural oxidative balance. On the other hand, ageing phenomena are the main cause of skin barrier damages, leading to a disequilibrium in the physiological redox system. Thus, the necessity to find new innovative cosmetic means, such as biodegradable non-woven tissues able to load, carry and release active ingredients in the right skin layers. These innovative cosmetic tissues can not only protect the skin from toxic environmental agents, but may balance the natural skin barrier, also acting as anti-aging agents when their fibers are bound to the right ingredients. The proposed tissues, consisting of polysaccharide natural fibers made of chitin nanofibrils and nanochitin, seem to be an ideal candidate for the production of new and effective biofunctional textiles, also because they are able to mimic the skin's extra cellular matrix (ECM) when electrospun. These innovative cosmeceuticals have shown the possibility of being used for food formulations as well as for topic anti-aging agents, having shown an interesting repairing effectiveness on skin and also on hair. Thus, they could be used both as active ingredient and as skin smart active carriers in substitution of normal emulsions, being also biodegradable, free of chemicals, and obtainable from waste material.

Chitin nanofibrils for advanced cosmeceuticals.

Chitin nanofibril is a new natural raw material obtained from crab and shrimp shells. It is a crystalline polysaccharide capable of interacting with enzymes, platelets, and other cell compounds present in living human tissue. From the first progress studies, it seems that chitin nanofibril helps to maintain cutaneous homeostasis and neutralize the activity of free radicals, and represents a natural carrier that favors the transcutaneous penetration of many active principles.