A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells.

Chimeric antigen receptor T cells (CAR T cells) with T stem (T) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human T cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RACCR7TCF1 T cell-like CAR T cells from both healthy donors and patients with cancer.

Eighty years of national mental health policy: Exploring the inclusion of a human rights approach.

Mental health, historically framed as the mere absence of mental health disorders, has led to unequal treatment, resulting in more persons living with mental health challenges. This limited framing of mental health, often woven into policy and practices across a broad range of governance structures, programs, and services, has led to individual and collective discrimination and structural and systemic inequities, culminating in the infringement of fundamental human rights. Using a broader framework for viewing mental health (e.

Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen.

Methyl-lysine reader p53 binding protein 1 (53BP1) is a central mediator of DNA break repair and is associated with various human diseases, including cancer. Thus, high-quality 53BP1 chemical probes can aid in further understanding the role of 53BP1 in genome repair pathways. Herein, we utilized focused DNA-encoded library screening to identify the novel hit compound UNC8531, which binds the 53BP1 tandem Tudor domain (TTD) with an IC of 0.

Discovery of hit compounds for methyl-lysine reader proteins from a target class DNA-encoded library.

Methyl-lysine (Kme) reader domains are prevalent in chromatin regulatory proteins which bind post-translational modification sites to recruit repressive and activating factors; therefore, these proteins play crucial roles in cellular signaling and epigenetic regulation. Proteins that contain Kme domains are implicated in various diseases, including cancer, making them attractive therapeutic targets for drug and chemical probe discovery. Herein, we report on expanding the utility of a previously reported, Kme-focused DNA-encoded library (DEL), UNCDEL003, as a screening tool for hit discovery through the specific targeting of Kme reader proteins.

COVID-19 Vaccine-Related Arthritis: A Descriptive Study of Case Reports on a Rare Complication.

Large-scale coronavirus disease 2019 (COVID-19) vaccination programs have been rolled out worldwide. Vaccines that are widely used globally include mRNA vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. COVID-19 vaccines can lead to varying side effects.