Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increases translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T cell clustering amplifies cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induces functional T cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T cell antitumor activity.

Whole-food phytochemicals antioxidative potential in alloxan-diabetic rats.

BACKGROUND: The importance of whole-food antioxidants in terms of promoting antioxidant recycling in the body in complex human diseases is not fully understood. We aim to discuss the benefits of whole-food antioxidants in ameliorating the diabetic complications in vivo and to address the effect of germination versus heat processing or drying on the potential therapeutic effect of whole grains and legumes. We studied the antioxidant status of alloxan-diabetic (AD) male Spargue Dawley rats, injected intraperitoneally with alloxan dose of 150 mg/kg body weight, and fed on experimental diets based on the flour of soybean, broadbean and whole-wheat for five weeks. RESULTS: Diabetes-induced oxidative stress in liver was manifested by significant increase in hepatic malondialdehyde (MDA), erythrocytes superoxide dismutase (eSOD) and plasma alpha-tocopherol (α-T) levels, reduction in hepatic glutathione (GSH) levels and catalase (CAT) activity. Consumption of soybean and whole-wheat both had beneficial effects on the oxidative status of AD rats more than broadbean. Feeding dried wheat was effective in improving MDA, GSH and α-T levels. Soybeans and wheat lowered triacylglycerols (TAGs) and tended to lower total cholesterol. Germination enhanced the effect of soybeans on TAGs and in the case of soy and wheat enhanced the effect on total cholesterol. CONCLUSION: Whole foods containing naturally occurring phytochemicals and antioxidant vitamins such as legumes and whole grains are recommended, alongside medication, for controlling hyperglycaemia, blood lipids and oxidative status in diabetes.