Recombinant P. auratus Insulin-like growth factor 1 receptor

Context The use of antibiotics in poultry production is appropriate; however, it brings a high risk of dissemination of antibiotic-resistant strains of pathogenic and non-pathogenic bacteria and their further transmission to humans via the food chain. Aims. The effects of supplementation with Lactobacillus acidophilus (a probiotic) or avilamycin (an in-feed antibiotic growth promoter), on growth performance, digestibility, plasma lipid levels, and the expression of certain growth-related genes were investigated. Methods. In total, 135 15-day-old broiler chicks were divided into three groups (n = 45): a control group and two treatment groups. Each treatment group was then further divided into three replicates (15 birds each). The control group was fed a basal diet; the second group received basal diet supplemented with avilamycin (0.1 g/kg); the third group received basal diet plus L. acidophilus (0.1 g/kg). Growth performance (bodyweight, feed intake and feed-conversion ratio) was measured. Digestibility and gene expression were measured at the end of the experiment. Key results. Greatest bodyweight gain was achieved in the L. acidophilus-fed chicks, which were significantly (P < 0.05) heavier than the control chicks and the avilamycin-fed chicks. Addition of avilamycin or L. acidophilus to the diet also significantly improved feed efficiency (P < 0.05) compared with the control. Although the digestibility of dry matter, crude protein and crude fibre significantly improved in the two experimental groups compared with the control, ether extract was not affected. In addition, plasma total cholesterol, triglyceride and low-density-lipoprotein cholesterol levels were significantly (P < 0.05) decreased whereas plasma high-density-lipoprotein cholesterol was significantly (P < 0.05) increased in the L. acidophilus group compared with the control. Expression of the genes for growth hormone secretagogue receptor (GHSR), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 1 receptor (IGF1R) was remarkably upregulated in the skeletal muscles of the two experimental groups. Conclusions. Supplementation with L. acidophilus (0.1 g/kg) in the broiler diet had positive effects on growth, feed intake, feed efficiency, digestibility, and plasma lipid levels of the broilers.

Background Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action. Methods The transcriptomes of primary tumours and metastases in mice harbouring ER+ breast cancer patient-derived xenografts (PDXs) were analysed following single-cell RNAseq. In vitro assays were employed to delineate mechanisms of endocrine resistance and stemness. Results A 16-gene phospho-Ser294 PR (p-PR) signature predicted poor outcome in ER+ breast cancer. Relative to primary PDX tumours, metastatic lesions expressed abundant p-PR and exhibited an activated PR gene programme with elevated expression of PGR and IRS-1. Breast cancer models of activated PR lost the expression of IGF1R and acquired insulin hypersensitivity with tamoxifen insensitivity. Activated p-PR+ breast cancer cells formed increased tumourspheres with enlarged ALDH+ and CD24-/CD44 populations. E2 induced PR/IRS-1 interaction and exchange of IGF1R beta for IRS-1 in p-PR-containing transcriptional complexes. Inhibition of IRS-1 or IR and inducible IRS-1 knockdown reduced tumourspheres. Endocrine-resistant models of luminal B breast cancer induced p-PR in 3D cultures and required PR and IRS-1 for tumoursphere formation. Conclusions Phospho-PR-B cooperates with IRS-1 to promote outgrowth of endocrine-resistant and stem-like breast cancer cells. Targeting phospho-PR/IRS-1 crosstalk may block the emergence of endocrine resistance.