Nrf2 Mitigates RANKL and M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been shown to be a negative regulator of osteoclast differentiation, but the precise mechanisms have not yet been established. We examined the precise roles of Nrf2 in regulating antioxidants and reactive oxygen species (ROS) levels, especially the cytoplasmic and mitochondrial ROS during osteoclastogenesis in vitro. In the current study, we found that the absence of promotes osteoclast differentiation in bone-marrow-derived macrophages (BMMs) and RAW 264.

Identification and validation of m6A-GPI signatures as a novel prognostic model for colorectal cancer.

In order to develop an N6-methyladenosine-related gene prognostic index (m6A-GPI) that can predict the prognosis in colorectal cancer (CRC), we obtained m6A-related differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) and m6Avar database, seven genes were screened by weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis. Then, m6A-GPI was constructed based on the risk score. Survival analysis indicated that patients in the lower m6A-GPI group have more prolonged disease-free survival (DFS), and different clinical characteristic groups (tumor site and stage) also showed differential risk scores.

Nfe2l1 deficiency mitigates streptozotocin-induced pancreatic β-cell destruction and development of diabetes in male mice.

Streptozotocin (STZ) is a pancreatic β cell-specific toxicant that is widely used to generate models of diabetes in rodents as well as in the treatment of tumors derived from pancreatic β cells. DNA alkylation, oxidative stress and mitochondrial toxicity have been recognized as the mechanisms for STZ-induced pancreatic β cell damage. Here, we found that pancreatic β cell-specific deficiency of nuclear factor erythroid-derived factor 2-related factor 1 (NFE2L1), a master regulator of the cellular adaptive response to a variety of stresses, in mice led to a dramatic resistance to STZ-induced hyperglycemia.

silenced insulinoma cells acquire aggressiveness and chemoresistance.

The transcription factor nuclear factor erythroid 2-like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific -knockout mice had hyperinsulinemia and that silencing of in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined.