In vitro fermentation and chemical characteristics of mediterranean by-products for swine nutrition

The purpose of the study is to determine the nutritional characteristics of some by-products derived from fruit juice and olive oil production to evaluate their use in pig nutrition. Five by-products of citrus fruit (three citrus fruit pulp and two molasses) and three by-products of olive oil (olive cake) obtained by different varieties are analysed for chemical composition. The fermentation characteristics are evaluated in vitro using the gas production technique with swine faecal inoculum. All the citrus by-products are highly fermentable, producing gas and a high amount of short-chain fatty acids. The fermentation kinetics vary when comparing pulps and molasses. Citrus fruit pulps show lower and slower fermentation rates than molasses. The olive oil by-products, compared to citrus fruits ones, are richer in NDF and ADL. These characteristics negatively affect all the fermentation parameters. Therefore, the high concentration of fiber and lipids represents a key aspect in the nutrition of fattening pigs. The preliminary results obtained in this study confirm that the use of by-products in pig nutrition could represent a valid opportunity the reduce the livestock economic cost and environmental impact

The human tumor suppressor ARF interacts with Spinophilin/Neurabin II, a type 1 protein-phosphatase-binding protein

The INK4a gene, one of the most often disrupted loci in human cancer, encodes two unrelated proteins, p16(INK4a) and p14(ARF) (ARF) both capable of inducing cell cycle arrest. Although it has been clearly demonstrated that ARF inhibits cell cycle via p53 stabilization, very little is known about the involvement of ARF in other cell cycle regulatory pathways, as well as on the mechanisms responsible for activating ARF following oncoproliferative stimuli. In search of factors that might associate with ARF to control its activity or its specificity, we performed a yeast two-hybrid screen. We report here that the human homologue of spinophilin/neurabin II, a regulatory subunit of protein phosphatase 1 catalytic subunit specifically interacts with ARF, both in yeast and in mammalian cells. We also show that ectopic expression of spinophilin/neurabin II inhibits the formation of G418-resistant colonies when transfected into human and mouse cell lines, regardless of p53 and ARF status. Moreover, spinophilin/ARF coexpression in Saos-2 cells, where ARF ectopic expression is ineffective, somehow results in a synergic effect. These data demonstrate a role for spinophilin in cell growth and suggest that ARF and spinophilin could act in partially overlapping pathway

Nutritive value and in vitro methane production of two perennial grasses under different stocking rates in periurban areas of West-Africa

Background. In sub-Saharan Africa, pasture is the most used practice in ruminant production, and grazing areas characteristics varied in different environment. To improve ruminants’ performances, the quality of forages represents one of the most important factors to keep under control. Objective. To quantify the effects of grazing stocking rate on the nutrient composition, energy content and in vitro fermentation characteristics including volatile fatty acids (VFA) and methane production (CH4) of two local perennial grasses Dactyloctenium aegyptium L. and Leptochloa caerulescens L. Methodology. The forage samples were collected in three locations (Zinvié, Gakpé, Adounko) characterized by different stocking rate (low, medium and high). Their chemical composition, energy content and in vitro fermentation characteristics, including CH4 production, were determined. Results. D. aegyptium showed the highest crude protein, energy content, organic matter degradability and VFA production (p<0.01) when collected in Zinvié, whereas the highest (p<0.01) structural carbohydrates (NDF) content was detected in Gakpé area and the highest CH4 production was recorded from the sample collected in Adounko (p<0.01). Contrariwise, L. caerulescens showed the highest level of crude protein and degradability (p<0.01) when collected in Zinvié, whereas it proved the highest NDF content and the lowest lignin values (p<0.01) when collected in Adounko. The highest CH4 level was obtained from the sample collected in area of Gakpé (p<0.01). Higher (p<0.01) in vitro VFA production were recorded in samples collected in Adounko and Gakpé than in the Zinvié. Implications. The results obtained in this study highlight the significant influence of urbanization and herd concentration, as well as of other environmental conditions, on the nutritional value and potential environmental impact of the studied perennial grasses. Conclusion. Samples from high grazing stocking rate locations produced more in vitro methane. Further in vivo studies are needed to confirm these results

Precision medicine and machine learning towards the prediction of the outcome of potential celiac disease

Potential Celiac Patients (PCD) bear the Celiac Disease (CD) genetic predisposition, a significant production of antihuman transglutaminase antibodies, but no morphological changes in the small bowel mucosa. A minority of patients (17%) showed clinical symptoms and need a gluten free diet at time of diagnosis, while the majority progress over several years (up to a decade) without any clinical problem neither a progression of the small intestine mucosal damage even when they continued to assume gluten in their diet. Recently we developed a traditional multivariate approach to predict the natural history, on the base of the information at enrolment (time 0) by a discriminant analysis model. Still, the traditional multivariate model requires stringent assumptions that may not be answered in the clinical setting. Starting from a follow-up dataset available for PCD, we propose the application of Machine Learning (ML) methodologies to extend the analysis on available clinical data and to detect most influent features predicting the outcome. These features, collected at time of diagnosis, should be capable to classify patients who will develop duodenal atrophy from those who will remain potential. Four ML methods were adopted to select features predictive of the outcome; the feature selection procedure was indeed capable to reduce the number of overall features from 85 to 19. ML methodologies (Random Forests, Extremely Randomized Trees, and Boosted Trees, Logistic Regression) were adopted, obtaining high values of accuracy: all report an accuracy above 75%. The specificity score was always more than 75% also, with two of the considered methods over 98%, while the best performance of sensitivity was 60%. The best model, optimized Boosted Trees, was able to classify PCD starting from the selected 19 features with an accuracy of 0.80, sensitivity of 0.58 and specificity of 0.84. Finally, with this work, we are able to categorize PCD patients that can more likely develop overt CD using ML. ML techniques appear to be an innovative approach to predict the outcome of PCD, since they provide a step forward in the direction of precision medicine aimed to customize healthcare, medical therapies, decisions, and practices tailoring the clinical management of PCD children

Mechanisms involved in the promoting activity of fibroblasts in HTLV-1-mediated lymphomagenesis: Insights into the plasticity of lymphomatous cells

Among the mechanisms leading to progression to Adult T-cell Leukaemia/Lymphoma in Human T-cell Leukaemia Virus type 1 (HTLV-1)-infected subjects, the contribution of stromal components remains poorly understood. To dissect the role of fibroblasts in HTLV-1-mediated lymphomagenesis, transcriptome studies, cytofluorimetric and qRT-PCR analyses of surface and intracellular markers linked to plasticity and stemness in coculture, and in vivo experiments were performed. A transcriptomic comparison between a more lymphomagenic (C91/III) and the parental (C91/PL) cell line evidenced hyperactivation of the PI3K/Akt pathway, confirmed by phospho-ELISA and 2-DE and WB analyses. C91/III cells also showed higher expression of mesenchymal and stemness genes. Short-term coculture with human foreskin fibroblasts (HFF) induced these features in C91/PL cells, and significantly increased not only the cancer stem cells (CSCs)-supporting CD10+GPR77+ HFF subpopulation, but also the percentage of ALDH1bright C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1bright C91/PL cells, downregulated mesenchymal and stemness genes in cocultured cells, and delayed lymphoma growth in immunosuppressed mice, thus hindering the supportive activity of HFF on CSCs. These data suggest that crosstalk with HFF significantly intensifies the aggressiveness and plasticity of C91/PL cells, leading to the enrichment in lymphoma-initiating cells. Additional research is needed to better characterize these preliminary findings

Circulating haematopoietic and endothelial progenitor cells are decreased in COPD

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD). Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean+/-sd 68+/-8 yrs; forced expiratory volume in one second: 48+/-12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8) were measured. Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3+/-2.5 versus 10.3+/-4.2 cells.microL-1), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30-50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-alpha levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies. In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity

Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy

Purpose Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the develop- ment of thyroid dysfunction during immunotherapy. Methods This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibi- tors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. Results Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibod- ies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). Conclusions Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs

Immunotherapy of brain metastases: breaking a "dogma"

Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases. Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events. Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting

Effects of a nutritional supplement in dogs affected by osteoarthritis

Osteoarthritis is a form of chronic joint inflammation caused by the deterioration of the joint cartilage, accompanied by chronic pain, lameness and stiffness, particularly after prolonged activity. Alternative treatments of canine osteoarthritis would be desirable and, recently nutraceuticals, have been proposed for this purpose. Twenty cross breed adult dogs affected by osteoarthritis were enrolled and equally divided into two groups (control vs. experimental). The nutritional supplement (Dynamopet srl, Verone, Italy) was administered for 90 days to the dogs of the experimental group in order to evaluate its metabolic and locomotor effects. All the clinical signs (lameness, pain on manipulation and palpation, range of motion and joint swelling) significantly (p < 0.01) improved during the trial as regards the experimental group. This group showed a significantly lower joint score than the control group (mean value 7.40 vs. 3.80). With regard to haematology, the mean corpuscular volume resulted significantly (p < 0.01) higher in the experimental group, i.e. alkaline phosphatase, cholesterol and triglycerides values decreased and were significantly (p < 0.01) lower than the control one, thus suggesting an improvement in bone remodelling and lipid metabolism. A decrease in the reactive oxygen metabolites and an increase in the biological antioxidant potential demonstrated an improvement in oxidative stress during the trial in the experimental group compare to the control group. Interleukins 6 decreased in the experimental group, while interleukins 10 resulted in the opposite trend. Moreover, the administration of up to 3 months of the studied supplement was well tolerated in the dogs and caused no adverse effects