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The effects of heather (composed primarily of Calluna vulgaris with a smaller content of Erica umbellata and Erica cinerea) consumption on the establishment of incoming infective larvae (experiment 1, preventive treatment) and an adult worm population (experiment 2, curative treatment) were investigated in Cashmere goats experimentally infected with Trichostrongylus colubriformis. In experiment 1, 12 castrated male goats were divided into two groups: heather-supplemented vs. non-supplemented animals. After 2 weeks of adaptation to the diet, all goats were experimentally infected per os with 6,000 T. colubriformis third-stage larvae. Three weeks post-infection, the goats were slaughtered, and worm counts as well as female worm fecundity and development were determined. Heather consumption was associated with a close to significant (P = 0.092) reduction (mean 14 %) in larvae establishment. No effect on fecundity was observed, but the length of female worms in supplemented goats was greater (P < 0.001). In experiment 2, 15 non-lactating does were experimentally infected with 6,000 T. colubriformis third-stage larvae. At 6 weeks post-infection, three groups were established: control, heather-supplemented and heather-supplemented with polyethylene glycol. Individual faecal nematode egg output was measured twice weekly to assess gastrointestinal nematode egg excretion. The goats were slaughtered 5 weeks after heather administration (11 weeks post-infection), and worm counts as well as female worm fecundity and development were subsequently determined. Heather administration was associated with a significant (P < 0.001) decrease (between 47 and 66 % compared with control group) in egg excretion from 45 to 76 days post-infection. Although worm counts and female fecundity were lower in supplemented goats, no significant differences were observed. Overall, the results showed a reduction in T. colubriformis larvae establishment and a decrease in nematode egg excretion when hea, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA, RTA2007-00098-C03), Depto. de Medicina y Cirugía Animal, Fac. de Veterinaria, TRUE, pub

Lipid and cholesterol metabolism play a crucial role in tumor cell behavior and in shaping the tumor microenvironment. In particular, enzymatic and non-enzymatic cholesterol metabolism, and derived metabolites control dendritic cell (DC) functions, ultimately impacting tumor antigen presentation within and outside the tumor mass, dampening tumor immunity and immunotherapeutic attempts. The mechanisms accounting for such events remain largely to be defined. Here we perturbed (oxy)sterol metabolism genetically and pharmacologically and analyzed the tumor lipidome landscape in relation to the tumor-infiltrating immune cells. We report that perturbing the lipidome of tumor microenvironment by the expression of sulfotransferase 2B1b crucial in cholesterol and oxysterol sulfate synthesis, favored intratumoral representation of monocyte-derived antigen-presenting cells, including monocyte-DCs. We also found that treating mice with a newly developed antagonist of the oxysterol receptors Liver X Receptors (LXRs), promoted intratumoral monocyte-DC differentiation, delayed tumor growth and synergized with anti-PD-1 immunotherapy and adoptive T cell therapy. Of note, looking at LXR/cholesterol gene signature in melanoma patients treated with anti-PD-1-based immunotherapy predicted diverse clinical outcomes. Indeed, patients whose tumors were poorly infiltrated by monocytes/macrophages expressing LXR target genes showed improved survival over the course of therapy. Thus, our data support a role for (oxy)sterol metabolism in shaping monocyte-to-DC differentiation, and in tumor antigen presentation critical for responsiveness to immunotherapy. The identification of a new LXR antagonist opens new treatment avenues for cancer patients.

Novel mixed matrix polymeric membranes were prepared by incorporating self-produced zinc oxide coated by polyaniline (ZnO-PANI) nanoparticles into polyethersulfone (PES) matrix using phase inversion method. Nanoparticles were synthesized, characterized and incorporated in PES matrix with loadings from 0.05 to 0.6 wt%. ZnO-PANI demonstrated effectiveness as a low-cost adsorbent, especially at a loading of 0.2 wt%. ZnO-PANI was used for adsorbing total phenolic compounds (TPC) from olive leaf extract (OLE) at different initial adsorbate concentration (49.92–466.59 mg/L) and pH (2−6). ZnO-PANI proved to be an effective and low-cost adsorbent to remove TPC from OLE. Langmuir model described the adsorption of TPC better than Freundlich model. Effect of incorporated nanoparticles on membranes morphology and hydrophilic properties studied using contact angle measurement, water content, membrane pore size and porosity, SEM, FTIR and pure water flux. Prepared membranes showed a significant increment in porosity, pore size and hydrophilicity by addition of ZnO-PANI in the casting solution up to 0.2 wt%. This led to a considerable improvement in permeability, which decreased with higher additive concentration. During OLE filtration tests (10–30 bar) using bare PES and 0.2 wt% ZnO-PANI/PES membranes, 0.2 wt% ZnO-PANI/PES showed the highest permeate flux and good TPC rejection (83–87%). Bare PES exhibited impressive TPC value rejections (85–92%) and better fouling resistance. Using 0.2 wt% ZnO-PANI achieved a balanced permeate flux and TPC rejection. The research emphasizes the practical applicability of these membranes in various industries due to their enhanced efficacy in removing phenolic compounds from natural extracts, offering a balanced approach between permeate flux and TPC rejection.