E. coli lacZ blocking peptide

Aims: Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. We aim to investigate the functional role of BAZ1A in regulating senescence in cancer and normal cells. Materials and methods: Knockdown of BAZ1A was performed via lentivirus mediated short hairpin RNA (shRNA) in various cancer cell lines (A549 and U2OS) and normal cells (HUVEC, NIH3T3 and MEF). A series of senescence-associated phenotypes were quantified by CCK-8 assay, SA-beta-Gal staining and EdU incorporation assay, etc. Key findings: Knockdown (KD) of BAZ1A induced series of senescence-associated phenotypes in both cancer and normal cells. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes in human cancer cells (A549 and U2OS). Significance: Our results revealed chromatin remodeling modulator BAZ1A acting as a novel regulator of cellular senescence in both normal and cancer cells, indicating a new target for potential cancer treatment.

Artificial organelles are envisioned as nanosized assemblies with intracellular biocatalytic activity to provide the host cells with non-native or missing/lost function. Hybrid vesicles loaded with glucose oxidase (NRGOx) or beta-galactosidase (NR beta-Gal) and equipped with lysosomal escape ability are assembled using phospholipids and the block copolymer poly(cholesteryl methacrylate)-block-poly(2-(dimethylamino)ethyl methacrylate). The co-localization of the building blocks and the catalytic activity of NRGOx and NR beta-Gal are illustrated. The intracellular activity of the nanoreactors in RAW 264.7 macrophages is confirmed by an enhanced reduction in viability for cells pre-incubated with NRGOx in the presence of glucose due to the generation of cytotoxic hydrogen peroxide compared to the controls. In addition, RAW 264.7 macrophages and primary human macrophages equipped with NR beta-Gal are able to intracellularly convert beta-Gal-NONOate into nitric oxide. The successful use of these hybrid vesicles to equip host macrophages with additional catalytic activity diversifies the available toolbox of nanocarriers with envisioned application in cell mimicry.