Using dried orange pulp in the diet of dairy goats: effects on milk yield and composition and blood parameters of dams and growth performance and carcass quality of kids

Although dried orange pulp (DOP) may conveniently replace cereals in ruminant diets, few studies have considered similar diet substitution for goats. We hypothesised that DOP could replace cereal-based concentrate in goat diets without detrimental effects on growth performance and carcass quality of suckling kids and milk performance and blood biochemical parameters of dams in early lactation. We also hypothesised that DOP substitution may increase the levels of antioxidants, such as phenolic compounds and vitamin E, in milk and improve its total antioxidant capacity (TAC). Therefore, 44 primiparous Payoya dairy goats were allocated to three experimental groups, each fed a different diet: control (CD, n = 14) based on a commercial concentrate with alfalfa hay as forage; and DOP40 (n = 16) in which 40% and DOP80 (n = 14) in which 80% of the cereal in the concentrate were replaced by DOP. The experiment lasted from the final month of pregnancy to 55 days postpartum. The DOP diets did not affect suckling kids’ carcass quality, but at 28 days, led to improvement in live weight (LW) and average daily gain (ADG) from birth, although no differences were found between DOP40 and DOP80 (for CD, DOP40 and DOP80, LW at 28 days was 8.00, 8.58 and 8.34 kg and ADG was 184, 199 and 195 g/day, respectively). Diet had no significant effect on milk yield (average daily milk yield and total yield at 55 days were 1.66 l/day and 90.6 l, respectively) and commercial and fatty acid composition. Nevertheless, α-tocopherol, total phenolic compound (TPC) and TAC concentration in milk increased with substitution of cereals by DOP (for CD, DOP40 and DOP80, concentration of α-tocopherol was 21.7, 32.8 and 42.3 μg/100 g, TPCs was 63.5, 84.1 and 102 mg gallic acid equivalents/l, and TAC was 6.63, 11.1 and 12.8 μmol Trolox equivalents/ml, respectively). Every plasma biochemistry parameter considered was within reference values for healthy goats; therefore, no pathological effect was detected for these variables due to dietary treatment. However, DOP diets caused a reduction in plasmatic creatine kinase and aspartate aminotransferase, implying reduced oxidative damage to muscles. In conclusion, DOP may be an interesting alternative to cereals in early lactation goat diets for increasing farmers’ income and the healthy antioxidant capacity of milk

Preclinical Efficacy of Endoglin-Targeting Antibody-Drug Conjugates for the Treatment of Ewing Sarcoma.

Endoglin (ENG; CD105) is a coreceptor of the TGFβ family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFβ, and as a soluble matricellular protein (sENG) when cleaved by matrix metalloproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease. We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody-drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma. Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line-derived xenografts and patient-derived xenografts in a dose-dependent manner. Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma