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Several human skin diseases are associated with fungi as dermatophytes and Malassezia. Skin mycoses are increasing and new alternatives to conventional treatments with improved efficacy and/or safety profiles are desirable. For the first time, the anti-dermatophytes and the anti-Malassezia activities of Vitis vinifera seed extracts obtained from different table and wine cultivars have been evaluated. Geometric minimal inhibitory concentration ranged from 20 to 97 µg/mL for dermatophytes and from 32 to 161 µg/mL for Malassezia furfur. Dried grape seed extracts analyzed by HPLC/DAD/ESI/MS showed different quali–quantitative compositions in terms of monomeric and polymeric flavan-3-ols. The minimal inhibitory concentrations for Trichophyton mentagrophytes and for M. furfur were inversely correlated with the amount of the polymeric fraction (r = −0.7639 and r = −0.7228, respectively). Differently, the antifungal activity against T. mentagrophytes was not correlated to the content of flavan-3-ol monomers (r = 0.2920) and only weakly correlated for M. furfur (r = −0.53604). These results suggest that extracts rich in polymeric flavan-3-ols, recovered from V. vinifera seeds, could be used for the treatment of skin fungal infections. Copyright © 2016 John Wiley & Sons, Ltd.

L-cysteine is currently recognized as a conditionally essential sulphur amino acid. Besides contributing to many biological pathways, cysteine is a key component of the keratin protein by its ability to form disulfide bridges that confer strength and rigidity to the protein. In addition to cysteine, iron represents another critical factor in regulating keratins expression in epidermal tissues, as well as in hair follicle growth and maturation. By focusing on human keratinocytes, the aim of this study was to evaluate the effect of cysteine supplementation as nutraceutical on keratin biosynthesis, as well as to get an insight on the interplay of cysteine availability and cellular iron status in regulating keratins expression in vitro. Herein we demonstrate that cysteine promotes a significant up-regulation of keratins expression as a result of de novo protein synthesis, while the lack of iron impairs keratin expression. Interestingly, cysteine supplementation counteracts the adverse effect of iron deficiency on cellular keratin expression. This effect was likely mediated by the up-regulation of transferrin receptor and ferritin, the main cellular proteins involved in iron homeostasis, at last affecting the labile iron pool. In this manner, cysteine may also enhance the metabolic iron availability for DNA synthesis without creating a detrimental condition of iron overload. To the best of our knowledge, this is one of the first study in an in vitro keratinocyte model providing evidence that cysteine and iron cooperate for keratins expression, indicative of their central role in maintaining healthy epithelia.

Chemical investigation of the Mediterranean ascidian A. conicum resulted in the isolation of two new meroterpenes, the conithiaquinones A (1) and B (2), in addition to two previously reported chromenols (3 and 4) and conicaquinones (5 and 6). The structures of conithiaquinones A and B were determined by interpretation of spectroscopic data, and regiochemical and stereochemical assignments were achieved with the aid of computational methods, including the recently developed DP4 NMR spectral prediction method. Both conithiaquinones A and B showed significant effects on the growth and viability of cells, with 1 showing interesting cytotoxicity against human breast cancer cells.

Cell suspension cultures of Vitis vinifera L., particularly after elicitation, have shown the ability to biosynthesize several stilbenoids. In this work the application of specific tandem mass spectrometry (MS/MS) experiments and the integration with data from UV-vis spectra, available only for the main compounds of the extract, allowed the detection of over 20 different stilbenoids. Up to eight monoglicosides, both monomers and dimers, a high number of dimer forms (up to 17), belonging to the group of viniferins and to their oxidized derivatives, were identified in the extract of Malvasia cell cultures. Moreover, the selectivity and sensitivity of the method allowed detection also of a few cis derivatives (up to 3) present in very low concentrations and presumably produced by the light exposure during treatment of the sample. To the best of the authors' knowledge, there are no literature data on MS/MS experiments targeted to simultaneously study monomeric and dimeric stilbenoids, both as free and glycosilated forms, in a complex mixture from V. vinifera cell suspension cultures.

Il ferro e il metallo di transizione piu abbondante nel sistema nervoso centrale in quanto cofattore di enzimi eminici e non-eminici coinvolti nel metabolismo energetico cellulare. Questo metallo e, inoltre, coinvolto nella sintesi di numerosi neurotrasmettitori, nella produzione della mielina e nello sviluppo delle ramificazioni dendritiche. Tuttavia, quando presente in eccesso, il ferro puo catalizzare la generazione di specie radicaliche reattive dell’ossigeno (ROS) capaci di provocare danni irreversibili al tessuto cerebrale. La ferritina, la principale proteina di deposito del ferro, svolge un’importante funzione citoprotettiva limitando la produzione dei ROS indotta dal ferro. L’espressione di questa proteina e regolata principalmente a livello post-trascrizionale dall’azione di due proteine citosoliche, IRP1 ed IRP2 (Iron Regulatory Proteins), capaci di legare specifiche sequenze nucleotidiche, note come IREs (Iron responsiva Elements), localizzate nella regione 5’-UTR dei messaggeri della ferritina. Considerando la notevole vulnerabilita delle cellule cerebrali allo stress ossidativo indotto dal ferro, importante causa di diverse patologie neurodegenerative, scopo del lavoro della tesi di Dottorato e stato quello di analizzare, in cellule di origine cerebrale, i meccanismi molecolari che controllano la biosintesi della ferritina e l’eventuale effetto protettivo di questa proteina in risposta ai danni indotti dall’ipossia e dalla successiva riossigenazione. I risultati ottenuti mostrano che l’ipossia riduce sensibilmente l’attivita di RNA-binding di IRP1 nelle cellule gliali (astrociti di tipo-1 e cellule di glioma), laddove tale attivita risulta incrementata nelle cellule neuronali (neuroni corticali). In tutte le colture cellulari analizzate questi effetti risultano revertiti dalla successiva fase di riossigenazione (3 e 24 h). Inoltre, nelle cellule gliali si osserva un rapido incremento della sintesi di ferritina gia durante la fase di ipossia, mentre nei neuroni la sintesi di questa proteina incrementa tardivamente, solo nell’ultima fase di riossigenazione (24 h). L’analisi dei livelli degli mRNA codificanti per la ferritina suggerisce che la sintesi di questa proteina e regolata nei neuroni corticali, principalmente a livello trascrizionale, mentre nelle cellule gliali e controllata sia a livello trascrizionale che post-trascrizionale. La diversa regolazione dell’espressione della ferritina potrebbe spiegare la maggiore vulnerabilita dei neuroni corticali al danno ipossico rispetto alle cellule gliali. Infatti, l’esposizione dei neuroni corticali all’ipossia/riossigenazione determina una marcata compromissione dell’attivita ossido-reduttiva mitocondriale, una notevole perossidazione lipidica ed l’attivazione dei principali marcatori dell’apoptosi. Nelle stesse condizioni sperimentali, le cellule gliali non mostrano alcuna apprezzabile variazione della vitalita cellulare, ne perossidazione lipidica ne attivazione dell’apoptosi. La notevole vulnerabilita delle cellule neuronali al danno indotto dall’ipossia risulta significativamente attenuata dal pre-trattamento delle colture neuronali con apoferritina esogena. Questo risultato conferma il ruolo citoprotettivo esercitato dalla ferritina nella risposta cellulare alle condizioni di ridotta disponibilita di ossigeno.