Acute graft versus host disease 1976-2020: reduced incidence and predictive factors.

We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years (p < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively (p < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively (p < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% (p < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p < 0.001), a family mismatched donor (RR 1.31, p = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p = 0.001), donor age above 40 years (RR 1.27, p < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% (p < 0.0001) and survival was 47, 51, and 58% (p < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods.

Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line.

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma.

Reduction of acrylamide formation in fried potato chips by Aureobasidum pullulans L1 strain.

Acrylamide is a potential carcinogenic molecule formed during food heat processing at high temperature (Maillard reaction). In the present study, the ability of the yeast Aureobasidium pullulans to deplete the acrylamide precursor free asparagine in fresh potatoes was investigated. A. pullulans applied before final frying changes the free amino acid composition of potatoes, decreasing the content of free asparagine by 16% and reducing acrylamide by 83% in fried potatoes. Potato browning was also reduced by yeast treatment without negative drawbacks on chip taste. This yeast, commonly used in fruit postharvest disease control, can therefore also be applied in potato and bakery industries to reduce food acrylamide content.

Postharvest application of brassica meal-derived allyl-isothiocyanate to kiwifruit: effect on fruit quality, nutraceutical parameters and physiological response.

The use of natural compounds to preserve fruit quality and develop high value functional products deserves attention especially in the growing industry of processing and packaging ready-to-eat fresh-cut fruit. In this work, potential mechanisms underlying the effects of postharvest biofumigation with brassica meal-derived allyl-isothiocyanate on the physiological responses and quality of 'Hayward' kiwifruits were studied. Fruits were treated with 0.15 mg L-1 of allyl-isothiocyanate vapours for 5 h and then stored in controlled atmosphere (2% O2, 4.5% CO2) at 0 °C and 95% relative humidity, maintaining an ethylene concentration <0.02 µL L-1. The short- and long-term effects of allyl-isothiocyanate on fruit quality traits, nutraceutical attributes, glutathione content, antiradical capacity and the activity of antioxidant enzymes were investigated. The treatment did not influence the overall fruit quality after 120 days of storage, but interestingly it enhanced the ascorbic acid, polyphenols and flavan-3-ol content, improving the antioxidant potential of kiwifruit. The short-term effect of allyl-isothiocyanate was evidenced by an increase of superoxide dismutase activity and of oxidative glutathione redox state, which were restored 24 h after the treatment. The expression levels of genes involved in detoxification functions, ethylene, ascorbate and phenylpropanoid biosynthesis, were also significantly affected upon allyl-isothiocyanate application. These results suggest that allyl-isothiocyanate treatment probably triggered an initial oxidative burst, followed by an induction of protective mechanisms, which finally increased the nutraceutical and technological value of treated kiwifruits.