miR-92a-2-5p Regulates the Proliferation and Differentiation of ASD-Derived Neural Progenitor Cells.

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with abnormal behavior. However, the pathogenesis of ASD remains to be clarified. It has been demonstrated that miRNAs are essential regulators of ASD. However, it is still unclear how miR-92a-2-5p acts on the developing brain and the cell types directly. In this study, we used neural progenitor cells (NPCs) derived from ASD-hiPSCs as well as from neurotypical controls to examine the effects of miR-92a-2-5p on ASD-NPCs proliferation and neuronal differentiation, and whether miR-92a-2-5p could interact with genetic risk factor, DLG3 for ASD. We observed that miR-92a-2-5p upregulated in ASD-NPCs results in decreased proliferation and neuronal differentiation. Inhibition of miR-92a-2-5p could promote proliferation and neuronal differentiation of ASD-NPCs. DLG3 was negatively regulated by miR-92a-2-5p in NPCs. Our results suggest that miR-92a-2-5p is a strong risk factor for ASD and potentially contributes to neuropsychiatric disorders.

Adverse and unconventional reactions related to immune checkpoint inhibitor therapy for cancer.

Immunotherapy is an emerging method for the treatment of cancer. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoint pathways and release the body's anti-tumor immunity. They consist mainly of antibodies against cytotoxic T lymphocyte associated antigen-4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death ligand 1 (PD-L1). Although ICI therapy has been shown to be effective at treating cancer, it can also destroy immune tolerance and lead to organ toxicity. These unwanted side effects are known as immune related adverse events (irAEs). ICI treatment can also cause unconventional reactions such as pseudoprogression and hyperprogression. Pseudoprogression looks like an increase in the tumor parenchyma but is actually a temporary inflammation in the tumor; hyperprogression refers to the acceleration of tumor growth after the start of immunotherapy. Understanding the mechanisms of these two phenomena and distinguishing their differences are necessary for the effective prevention and treatment of unconventional reactions.