The fruit of the pomegranate (Punica granatum L.) is an important nutraceutical food rich in polyphenolic compounds, including hydrolysable tannins, anthocyanins and flavonols. Their composition varies according to cultivar, tissue and fruit development stage and is probably regulated by a combination of MYB and bHLH type transcription factors (TFs). In this study, metabolomics analysis during fruit developmental stages in the main pomegranate cultivars, Wonderful and Valenciana with contrasting colour of their ripe fruits, showed that flavonols were mostly present in flowers while catechins were highest in unripe fruits and anthocyanins in late fruit maturation stages. A novel MYB TF, PgMYB5-like, was identified, which differs from previously isolated pomegranate TFs by unique C-terminal protein motifs and lack of the amino-acid residues conserved among anthocyanins promoting MYBs. In both pomegranate cultivars the expression of PgMYB5-like was high at flowering stage, while it decreased during fruit ripening. A previously identified bHLH-type TF, PgbHLH, also showed high transcript levels at flowering stage in both cultivars, while it showed a decrease in expression during fruit ripening in cv. Valenciana, but not in cv. Wonderful. Functional analysis of both TFs was performed by agroinfiltration into Nicotiana benthamiana leaves. Plants infiltrated with the PgMYB5-like+PgbHLH combined construct showed a specific and significant accumulation of intermediates of the flavonoid pathway, especially dihydroflavonols, while anthocyanins were not produced. Thus, we propose a role for PgMYB5-like and PgbHLH in the first steps of flavonoid production in flowers and in unripe fruits. The expression patterns of these two TFs may be key in determining the differential flavonoid composition in both flowers and fruits of the pomegranate varieties Wonderful and Valenciana.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

Cardoon (Cynara cardunculus L.) is a Mediterranean crop, member of the Asteraceae family, characterized by high production of biomass and secondary metabolites and by a good adaptation to climate change, usable in green chemistry, nutraceutical, and pharmaceutical sectors. Recent studies demonstrated the ability of cardoon to grow up in a stressful environment, which is associated with enhanced biosynthesis of biologically active compounds in these plants, and this effect is increased by abiotic stresses (salt, heat, pollution, and drought stress) that characterize many world marginal areas, affected by the climate changes. The plant response to these stresses consists in implementing different processes that modify some plant biological functions, such as alleviating both cellular hyperosmolarity and ion disequilibrium or synthesizing antioxidant molecules. The aim of this work was to investigate different cardoon response mechanisms to abiotic stresses and to evaluate their influence on the biologically active compounds biosynthesis. Following this purpose, we analyzed the ability of cardoon seeds to germinate under different salt stress conditions, and on the sprouts obtained, we measured the total phenol content and the antioxidant activity. Moreover, the growth of cardoon seedlings grown under heavy metals stress conditions was monitored, and the expression levels of heavy metal transport-associated genes were analyzed. The results showed the ability of cardoon plants to tolerate abiotic stress, thanks to different defense mechanisms and the possibility to obtain biomass with high content of biologically active molecules by exploiting the natural tolerance of this species for abiotic stresses. Moreover, we identified some important genes encoding for metal transportation that may be involved in arsenic and cadmium uptake and translocation in C. cardunculus. Then, this species can be considered as a promising crop for green chemistry and energy in marginal lands.

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During the spread of COVID-19, many laboratories used the “Formulation 1” proposed by the World Health Organization to prepare hand sanitizers. Taking into consideration its ingredients and the prolonged use of hand sanitizers, “Formulation 1” (P1) was compared with two gel formulations (P2 and P3) prepared with the addition of natural emollients and two different viscosity enhancers to define their chemical–physical stability, biocidal efficacy, and in vivo acceptability and tolerability. P1 resulted in the most efficient biocide but was poorly tolerated by the skin and not acceptable in volunteer hedonic evaluation, especially in terms of irritation and drying effect, with an expectable reduction in the compliance. Moreover, its liquid formulation is unpractical and can cause ethanol evaporation. P2 and P3 proved to be both good products regarding pH and alcohol strength values. However, in terms of viscosity, texture, ease of use, and application, P3 seemed to be a better gel product than P2. Moreover, they were well tolerated by the skin, increasing the hydration of the stratum corneum, due to the addition of Calendula officinalis and Aloe vera. Despite a lower ethanol concentration than P1, P2 and P3 also showed a good biocide efficiency, with better results in P2. In conclusion, these gel formulations proved to be more convenient for long-term use with a good balance between efficacy, safety, and compatibility with the skin.