Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.
View Article and Find Full Text PDFBackground: Chronic kidney disease (CKD) has emerged as a substantial global health challenge, with a marked rise in associated mortality. However, it often goes undetected until advanced stages, particularly in low-income and middle-income countries such as South Africa. We investigated the prevalence and progression of CKD in South Africa, utilising a subset of data from the National Health Laboratory Services Multi-morbidity Cohort.
View Article and Find Full Text PDFPIK-75 (F7) is a potent multikinase inhibitor that targets p110α, DNA-PK, and p38γ. PIK-75 has shown potential as a therapy in preclinical cancer models, but it has not been used in the clinic, at least in part, due to limited solubility. We therefore developed a nanoparticle to encapsulate PIK-75 and enable targeted cellular delivery.
View Article and Find Full Text PDFBackground: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.
View Article and Find Full Text PDFPsychological distress can have a significant impact on cardiovascular disease (CVD) and efforts to treat psychological distress may improve CVD risk factors. Therefore, we conducted a retrospective feasibility of implementation study to assess the utilization of short-term psychotherapy in patients engaged in a cardiovascular prevention program. Participants included patients engaged in the Women's Health or Preventive Cardiology programs from January 2019 to June 2022.
View Article and Find Full Text PDF