Evaluation of fodder legumes for nutraceutical, pharmaceutical and cosmetic applications

Since the beginning of human cultivation, the role of plants in medicine has been of huge importance. The aim of this PhD Project is to investigate some forage plants belonging to the family of Fabaceae to gain knowledge concerning their possible use in nutraceutical, pharmaceutical and cosmetics field. These plants have been chosen because they are characterized by great productive potential, but they are still under-exploited from the officinal and industrial point of view. They are also a potential source for the extraction of bioactive compounds with possible pharmaceutical and cosmetic applications (Rodrigues et al., 2013;Cornara et al., 2016), being generally rich in secondary metabolites such as alkaloids, amines, flavonoids, coumarins, condensed tannins and saponins (Burlando et al., 2010; Pastorino et al., 2017) To increase their use also in the industrial sector and, consequently, their commercial value, the study has focused on the identification of bioactive compounds with possible interest in human health. In this study a multidisciplinary approach was carried out, investigating several aspects such as antioxidant, antilipidemic and cytotoxicity strength, content of total phenols and flavonoids. In this PhD Project we studied four species of legumes: Melilotus officinalis (L.) Pall., Lespedeza capitata Michx., Sulla coronaria (L.) Medik and Glycyrrhiza glabra L. Thanks to a collaboration with Egadi S.r.l., Favignana, Italy, we also concentrated our study to another kind of plant, belonging to the family of Potamogetonaceae: Posidonia oceanica (L.) Delile. The species has shown bioactivities suitable for the development of cosmetic and dermatologic applications. In summary, the results of these investigations show new opportunities to exploit the plants studied plants in bioindustry processes, possibly increasing their commercial value

Patient-Derived Xenografts of Non Small Cell Lung Cancer: Resurgence of an Old Model for Investigation of Modern Concepts of Tailored Therapy and Cancer Stem Cells

Current chemotherapy regimens have unsatisfactory results in most advanced solid tumors. It is therefore imperative to devise novel therapeutic strategies and to optimize selection of patients, identifying early those who could benefit from available treatments. Mouse models are the most valuable tool for preclinical evaluation of novel therapeutic strategies in cancer and, among them, patient-derived xenografts models (PDX) have made a recent comeback in popularity. These models, obtained by direct implants of tissue fragments in immunocompromised mice, have great potential in drug development studies because they faithfully reproduce the patient's original tumor for both immunohistochemical markers and genetic alterations as well as in terms of response to common therapeutics They also maintain the original tumor heterogeneity, allowing studies of specific cellular subpopulations, including their modulation after drug treatment. Moreover PDXs maintain at least some aspects of the human microenvironment for weeks with the complete substitution with murine stroma occurring only after 2-3 passages in mouse and represent therefore a promising model for studies of tumor-microenvironment interaction. This review summarizes our present knowledge on mouse preclinical cancer models, with a particular attention on patient-derived xenografts of non small cell lung cancer and their relevance for preclinical and biological studies

The bioactivity of Hedysarum coronarium extracts on skin enzymes and cells correlates with phenolic content

CONTEXT: The search for bioactive compounds from botanical sources is attracting much interest. However, differences in chemical composition may occur within the same species depending on different geographical origins. OBJECTIVES: We evaluated the properties on skin enzymes and cells of extracts from sulla legume crop Hedysarum coronarium L. (Fabaceae), collected at two Italian sites near Pisa and Ventimiglia, for possible dermatological and cosmetic applications. MATERIAL AND METHODS: Plant aerial portions were extracted in MTBE/ethyl acetate/acetone, obtaining two extracts named Pisa sulla extract (PSE) and Ventimiglia sulla extract (VSE). Extracts were subjected to chemical characterization, LC-MS/MS analysis and biological assays. RESULTS: PSE showed stronger antiradical scavenging and higher phenolic and flavonoid contents with respect to VSE. LC-MS/MS analysis revealed similar composition for the two extracts, but PSE was richer in condensed tannins and flavonoids, principally rhoifolin, quercetin, naringenin and derivatives. PSE induced stronger inhibition on collagenase and elastase by in vitro enzyme assays, possibly due to higher levels of condensed tannins and quercetin. ELISA bioassay on human dermal fibroblasts revealed stronger PSE induction of collagen production. Determination of glycerol release from adipocytes disclosed stronger stimulation of lipolysis by PSE, allegedly ascribed to higher charge of quercetin and derivatives. In summary, the higher richness in phenolics of PSE is strictly related to stronger bioactivity. DISCUSSION AND CONCLUSIONS: Data indicate that aerial H. coronarium material is suitable for the development of dermatological and cosmeceutical products, but the geographical origin is an important factor for maximally exploiting the biological properties of this species

Changes in Serum Blood Parameters in Farmed Rainbow Trout (Oncorhynchus mykiss) Fed with Diets Supplemented with Waste Derived from Supercritical Fluid Extraction of Sweet Basil (Ocimum basilicum)

The antimicrobial and immunostimulant proprieties of aromatic plant extracts have been widely described, but their effects on serum blood biochemistry in fish have not. For this study, we assessed the changes in serum blood biochemical parameters in rainbow trout fed with a fish diet supplemented with a basil supercritical extract (F1-BEO). Our hypothesis was that treatment and time would be associated with changes in 10 serum blood biochemical parameters. F1-BEO was added to a commercial feed (0.5, 1, 2, 3% w/w). The fish were fed for 30 days, and the blood samples were collected at 2 time points (15 and 30 days). A two-way ANOVA showed a significant effect of treatment, time, and interaction treatment × time on creatinine, urea, total protein, albumin, magnesium, and phosphorus (p < 0.05), a significant effect of both time and interaction treatment × time on cholesterol (CHOL), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels, and a significant effect of time on triglycerides (p < 0.05). While changes in several of the parameters were observed, the levels remained within the normal range for rainbow trout. Notably, after 30 days there was a significant decrease in CHOL in fish treated with 0.5% and 1% w/w F1-BEO (p < 0.05). The statistically non-significant increase in GOT and GPT in the fish fed with F1-BEO up to 3% w/w indicated a positive effect of basil on liver health. Our findings suggest a potential use for basil extracts (for example., F1-BEO) in fish feed to reduce antibiotic use and improve fish welfare.This research was funded by Italian Ministry of Health, Ricerca Finalizzata, grant number GR-2013-02355796.Peer reviewe

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Bilateral salpingo-oophorectomy versus GnRH analogue in the adjuvant treatment of premenopausal breast cancer patients : cost-effectiveness evaluation of breast cancer outcome, ovarian cancer prevention and treatment

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. METHODS: A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. RESULTS: Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. CONCLUSION: Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered

Recent and subfossil diatom assemblages as indicators of environmental change (including fish introduction) in a high-mountain lake

We investigated modern-littoral and subfossil sediment-core diatoms in the shallow (max depth 6.4 m) high mountain Lake Balma in the Orsiera Rocciavr`e Nature Park (Italian Western Alps). Our study provided evidence that might be related to the response of diatom assemblages to fish introduction, in particular the decreasing of the nutrient-enrichment sensitive low-profile life-form/ecological guild and the increase in species known to react positively to the augmented nutrient availability due to fish excretions (e.g., Fragilaria nanana, Pseudostaurosira brevistriata, Staurosirella neopinnata). We are, however, aware that some of these effects could as well have been caused by pastures and cattle watering, and by increased temperatures due to global warming, and we acknowledge the typical complex-interaction pattern among different stressors. High-mountain lakes are \u2018\u2018early warning systems\u2019\u2019 for the whole alpine system and can contribute valuable information also on the interactions between environmental global changes and anthropogenic impacts. Benthic diatoms, in particular, can provide useful indications on the deleterious effects of non-native fish introduction, cattle grazing, and global warming, and thus support an adaptive and sustainable management of high-mountain lakes for the sake of nature conservation