Production of stilbenes in callus cultures of the Maltese indigenous grapevine variety, Ġellewża

The production of secondary metabolites in tissue culture has been considered as an alternative to the cultivation and harvesting of crops intended for this purpose. The present study was aimed at the growth of callus and production of polyphenolic compound of callus derived from a Maltese indigenous grapevine variety, Ġellewża. Callus was inoculated onto plant growth regulators-enriched Murashige Skoog media (MSm) to determine whether polyphenols are produced in vitro as well as to determine the best combination of plant growth regulators needed for the production of these metabolites. From results obtained, it was observed that the best callus production was obtained by auxin-enriched MSm. In fact, indole acetic acid and indole acetic acid /6-benzyl aminopurine enhanced biomass accumulation (3.04 g and 3.39 g) as opposed to the others (<1.97 g). On the other hand, parameters showing the presence of flavonoids (tonality, 3.80), particularly anthocyanins (24.09 mg/kg) and total polyphenols (1.42 mg/g), were optimum in the presence of cytokinins, particularly 6-benzyl aminopurine. Analysis for single polyphenols revealed a high amount a particular stilbene: polydatin (glucoside of resveratrol). Resveratrol and other typical polyphenols, found in mature berries, were also found in significant quantities, while the other polyphenolic compounds were found in minimal quantities. This is the first study to describe the production and composition of polyphenols in Ġellewża callus cultures. From the results obtained, it can be seen that this grape tissue is an excellent alternative for the production of polyphenols from the stilbene group, which can be upscaled and exploited commercially.This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant no.172017) and by the Malta Council for Science and Technology (Research and Innovation Special Project 2008-01-VOTIVVOM-Valorization of the indigenous vine varieties of Malta: Conservation, Assessment and Innovation [R&I-SP-2008-01]).peer-reviewe

Supplementary data for article: Bonello, M.; Gašić, U.; Tešić, Ž.; Attard, E. Production of Stilbenes in Callus Cultures of the Maltese Indigenous Grapevine Variety, Gellew Za. Molecules 2019, 24 (11). https://doi.org/10.3390/molecules24112112

Supplementary material for: [https://doi.org/10.3390/molecules24112112]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3711

The Role of Monoclonal Antibodies in the First-Line Treatment of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma

Elderly transplant-ineligible (NTE) patients represent the majority of patients affected by multiple myeloma (MM). Elderly patients are a highly heterogeneous population, with large variability in health and functional status. Thus, choosing their optimal treatment is challenging. A wide range of first-line treatments is available, and novel-agent combinations, including monoclonal antibodies (mAbs), have recently entered clinical practice. The combination of the anti-CD38 mAb daratumumab with bortezomib, melphalan and prednisone (Dara-VMP) or lenalidomide and dexamethasone (Dara-Rd) demonstrated impressive advantages in terms of progression-free survival and minimal residual disease negativity, as compared to VMP and Rd, without safety concerns. Another anti-CD38 mAb, isatuximab, is showing encouraging results, and new isatuximab-based combinations might enter clinical practice in the future. Nevertheless, available data come from clinical trials with selected patient populations and, to date, the manageability of these regimens in real-life patients or in frail patients remains unknown. Frailty-tailored treatments, including mAbs, are under evaluation in preliminary studies. In this review, we analyze recently approved mAb-based treatments for NTE newly diagnosed MM patients and new combinations under evaluation, focusing on the efficacy and safety of these regimens and on open issues regarding the choice of therapy for elderly patients