Effect of different pastures on CLA content in milk and sheep cheese

It is known that milk composition included conjugated linoleic acid (CLA) is affected by animal feeding system (Cabiddu et al., 2001). In Sardinia dairy sheep feeding is mainly based on pastures. Most of them are characterised by self-regenerating species, like annual ryegrass (Lolium rigidum Gaudin) and burr medic (Medicago polymorpha L.). Non conventional species belonging to the Compositae family such as (Chrysanthemum coronarium L.) seem interesting for sheep feeding when other herbages decrease in quality (late spring- early summer). It was observed that C. coronarium establishes rapidly, can be grazed early in the growing season and persist where other pasture species may disappear; for these reasons it can be considered a valuable source of food. Moreover a preliminary study with dairy sheep fed fresh forage of C. coronarium showed relatively high levels of CLA in milk (Molle G. pers. com.) The aim of the present work was to study the influence of different pastures on milk composition, with particular reference to CLA and its precursors

A gas chromatography-mass spectrometry-based metabolomic approach for the characterization of goat milk compared with cow milk

In this work, the polar metabolite pool of commercial caprine milk was studied by gas chromatography-mass spectrometry and multivariate statistical data analysis. Experimental data were compared with those of cow milk and the discriminant analysis correctly classified milk. By the same means, differences due to heat treatments (UHT or pasteurization) on milk samples were also investigated. Results of the 2 discriminant analyses were combined, with the aim of finding the discriminant metabolites unique for each class and shared by 2 classes. Valine and glycine were specific to goat milk, talose and malic acid to cow milk, and hydroxyglutaric acid to pasteurized samples. Glucose and fructose were shared by cow milk and UHT-treated samples, whereas ribose was shared by pasteurized and goat milk. Other discriminant variables were not attributed to specific metabolites. Furthermore, with the aim to reduce food fraud, the issue of adulteration of caprine milk by addition of cheaper bovine milk has been also addressed. To this goal, mixtures of goat and cow milk were prepared by adding the latter in a range from 0 to 100% (vol/vol) and studied by multivariate regression analysis. The error in the level of cow milk detectable was approximately 5%. These overall results demonstrated that, through the combined approach of gas chromatography-mass spectrometry and multivariate statistical data analysis, we were able to discriminate between milk typologies on the basis of their polar metabolite profiles and to propose a new analytical method to easily discover food fraud and to protect goat milk uniqueness. The use of appropriate visualization tools improved the interpretation of multivariate model results

Triazolopyridinyl-acrylonitrile derivatives as antimicrotubule agents: Synthesis, in vitro and in silico characterization of antiproliferative activity, inhibition of tubulin polymerization and binding thermodynamics

In this paper we report the synthesis, in vitro anticancer activity, and the experimental/computational characterization of mechanism of action of a new series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g, 7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to interesting antiproliferative activity against 9 different cancer cell lines derived from solid and hematological human tumors. Fluorescence-based assays prove that these molecules interfere with tubulin polymerization. Furthermore, isothermal titration calorimetry (ITC) provides full tubulin/compound binding thermodynamics, thereby ultimately qualifying and quantifying the interactions of these molecular series with the target protein. Lastly, the analysis based on the tight coupling of in vitro and in silico modelling of the interactions between tubulin and the title compounds allows to propose a molecular rationale for their biological activity

Benessere animale e riflessi sulla qualità delle produzioni

Le ricerche mirate a definire indicatori oggettivi di condizioni di stress e gli effetti sulle funzioni degli animali di allevamento rappresentano uno degli obiettivi prioritari delle produzioni animali, in quanto rispondono ad esigenze normative comunitarie, ad un miglioramento dell’efficienza degli allevamenti e ad aspettative dell’opinione pubblica. In questa rassegna sono raccolte alcune recenti esperienze che indicano come alcuni fattori alimentari e di allevamento siano in grado di condizionare la risposta biologica dei ruminanti da latte, ovini e bovini, e di influire quindi sulla qualità della vita degli animali e i riflessi che sulla qualità delle produzioni lattiero casearie. La complessità delle risposte dei sistemi biologici ad eventi ambientali di diverso tipo ed intensità, indica la necessità di un approccio multidisciplinare, in grado di integrare conoscenze di base, tipiche delle scienze biologiche, con quelle della fisiologia, della nutrizione e dei sistemi di allevamento

A gas chromatography-mass spectrometry untargeted metabolomics approach to discriminate Fiore Sardo cheese produced from raw or thermized ovine milk.

Thermization is a sub-pasteurization heat treatment of cheese milk (at 57-68°C for 15-30 s) aimed to reduce the number of undesirable microbial contaminants with reduced heat damage to the indigenous milk enzymes. In this work, the effects of milk thermization on the compositional parameters, proteolysis indices, free fatty acid levels, and low molecular weight metabolite profiles of ovine cheese were studied. Cheese samples at different ripening stages and produced in 2 different periods of the year were analyzed. While the effects of milk thermization on cheese macro-compositional parameters and free fatty acid levels were not evident due to the predominant effects of milk seasonality and cheese ripening stage, the gas chromatography-mass spectrometry based metabolomics approach of ovine cheese produced from raw and thermized milk highlighted strong differences at the metabolite level. Discriminant analysis applied to gas chromatography-mass spectrometry data provided an excellent classification model where cheese samples were correctly classified as produced from raw or thermized milk. The metabolites that mostly changed due to the thermization process belonged to the classes of free amino acids and saccharides. Gas chromatography-mass spectrometry-based metabolomics has proven to be a valid tool to study the effect of mild heat treatments on the polar metabolite profile in ovine cheese

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma

: Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

EFFICACY AND SAFETY OF BOCEPREVIR-BASED THERAPY IN HCVG1 TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED FIBROSIS/CIRRHOSIS: THE ITALIAN AND SPANISH NPP EARLY ACCESS PROGRAM

Background and Aims: To maximize cost/efficay of boceprevirbased triple therapy (BOC) in patients with HCV-related advanced fibrosis/cirrhosis. Methods: ITT SVR12, safety and futility rules value were evaluated in the multicenter national Italian and Spanish early access Name- Patient-Program which includes treatment-experienced patients with HCVG1-related advanced fibrosis/cirrhosis (Metavir F3/4) treated with BOC in both countries. Results: 402 patients (mean age 55 years; range 22–75), 316 (78.6%) G1b, 255 (63.4%) F4, 60 (30.9%) with oesophageal varices, 137 (34.1%) relapsers, 95 (23.6%) partial and 168 (41.8%) null responders were enrolled. Platelets count <100,000 and albumin levels <3.5 g/dl were present in 49 (12.2%) and 22 (6.3%) patients, respectively. 369 (91.8%) received at least 1 dose of BOC. Overall ITT SVR12 rates and according to prior response to P/R, fibrosis stage and TW8 HCV-RNA value to P/R/BOC are reported in the table. At multivariate analysis, the strongest predictors of SVR12 were TW8 HCV-RNA undetectability (RR, 30.8; 95% CI, 8.7–108.7) and HCV-RNA detectable but <1000 IU/mL (RR, 9.1; 95% CI, 2.6–31.8) compared to those with HCV-RNA ≥1000 IU/mL. Two patients (0.5%) died from multi-organ failure, 13 (3.2%) developed hepatic decompensation, 41 (10.2%) had severe anemia (<8.5 g/dl) and 31 (7.7%) required at least one blood transfusion. Conclusions: In treatment-experienced patients with advanced fibrosis/cirrhosis, SVR12 attained by BOC was satisfactory. Mortality, life-threatening adverse events and severe anemia rates were similar to those reported in other real-practice studies. A TW8 futility rule enables a safely discontinuation of BOC in patients who are extremely unlikely to achieve SVR, thus optimizing the effectiveness of treatment in this difficult-to-cure population

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19