Project description:Immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1 have shown remarkable antitumor efficacy but can also cause immune-related adverse events, including checkpoint inhibitor-induced liver injury (ChILI). This multi-omic study aimed to investigate changes in blood samples from treated cancer patients who developed ChILI. PBMCs were analyzed by transcriptomic and T cell receptor sequencing (bulk and single cell), and extracellular vesicle (EV) enrichment from plasma was analyzed by mass spectroscopy proteomics. Data were analyzed by comparing the ChILI patient group to the control group who did not develop ChILI and by comparing the onset of ChILI to pre-ICI treatment baseline. We identified significant changes in T cell clonality, gene expression, and protein levels in peripheral blood mononuclear cells (PBMCs) or plasma at the time of liver injury. Onset of ChILI was accompanied by an increase in T-cell clonality. Pathway analysis highlighted the involvement of innate and cellular immune responses, mitosis, pyroptosis, and oxidative stress. Single-cell RNA sequencing revealed that these changes were primarily found in select T cell subtypes (including CD8+ effector memory cells), while CD16+ monocytes exhibited enrichment in metabolic pathways. Proteomic analysis of plasma extracellular vesicles showed enrichment in liver-associated proteins among differentially expressed proteins. Interestingly, an increase in PBMC PD-L1 gene expression and plasma PD-L1 protein was also found to be associated with onset of ChILI.
Project description:Immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1 have shown remarkable antitumor efficacy but can also cause immune-related adverse events, including checkpoint inhibitor-induced liver injury (ChILI). This multi-omic study aimed to investigate changes in blood samples from treated cancer patients who developed ChILI. PBMCs were analyzed by transcriptomic and T cell receptor sequencing (bulk and single cell), and extracellular vesicle (EV) enrichment from plasma was analyzed by mass spectroscopy proteomics. Data were analyzed by comparing the ChILI patient group to the control group who did not develop ChILI and by comparing the onset of ChILI to pre-ICI treatment baseline. We identified significant changes in T cell clonality, gene expression, and protein levels in peripheral blood mononuclear cells (PBMCs) or plasma at the time of liver injury. Onset of ChILI was accompanied by an increase in T-cell clonality. Pathway analysis highlighted the involvement of innate and cellular immune responses, mitosis, pyroptosis, and oxidative stress. Single-cell RNA sequencing revealed that these changes were primarily found in select T cell subtypes (including CD8+ effector memory cells), while CD16+ monocytes exhibited enrichment in metabolic pathways. Proteomic analysis of plasma extracellular vesicles showed enrichment in liver-associated proteins among differentially expressed proteins. Interestingly, an increase in PBMC PD-L1 gene expression and plasma PD-L1 protein was also found to be associated with onset of ChILI.
Project description:The present study was conducted to investigate the effect of graded levels of black soldier fly larvae (BSFL) (Hermetia illucens) meal and BSFL paste in extruded diets for Atlantic salmon (Salmo salar). A total of 1260 Atlantic salmon with 34 g of mean initial weight were randomly distributed into 21 fiberglass tanks and fed (n=3) with seven extruded isolipidic and isonitrogenous diets for seven weeks. The experimental diets consisted of a positive control diet based on fishmeal, soy protein concentrate, corn gluten, faba bean and fish oil (Control_1); three diets with increased levels of full lipid BSFL meal, substituting 6.25% (6.25_IM), 12.5% (12.5_IM) and 25% (25_IM) of the protein content of Control_1; two diets with increased levels of full lipid BSFL paste, substituting 3.7% (3.7_IP) and 6.7% (6.7_IP); and of protein from Control_1 and a negative a control with 0.84 % of formic acid (Control_2). We investigate the effect of diets on growth performance, mmune response and health.
Project description:Transcription profiling by high throughput sequencing of wheat cultivar Chinese Spring seedlings maintained without phosphate for 10 days