Stephen Safe

1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) compounds in the presence or absence of a 4-hydroxylphenyl group bind both orphan nuclear receptor 4A1 (NR4A1) and NR4A2. In cancer cells, these compounds bind and inactivate …

Background/Objective: Coffee is the most highly consumed beverage worldwide, and coffee drinkers exhibit decreased mortality and protection from aging-related diseases. This study investigates the role of orphan nuclear receptor 4A1 (NR4A1)…

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and strom…

Orphan nuclear receptor 4A1 (NR4A1) is a member of the NR4A subfamily that was initially discovered as an intermediate early gene expressed in response to stressors, including inflammatory agents. This review addresses the hypothesis that N…

The nuclear receptor (NR) superfamily of ligand-activated receptors plays a key role in maintaining cellular homeostasis and in pathophysiology. NRs can be subdivided into functional activities structural similarity and the existence of end…

Polyfluoroalkyl substances (PFAS) are widely used industrial compounds that have been identified as contaminants in almost every component of the global ecosystem, and in human studies, higher levels of PFAS have been correlated with increa…

It was recently reported that the hydroxyflavones quercetin and kaempferol bind the orphan nuclear receptor 4A1 (NR4A1, Nur77) and act as antagonists in cancer cells and tumors, and they inhibit pro-oncogenic NR4A1-regulated genes and pathw…

Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis…

Piperlongumine and derivatives are being developed as anticancer agents which act primarily as inducers of reactive oxygen species (ROS) in cancer cell lines. Many of the anticancer activities of piperlongumine resemble those observed for b…

Resveratrol is a polyphenolic phytochemical found in fruits, nuts and vegetables that contributes to the remarkable dietary effects of polyphenolic as inhibitors aging and multiple aging related diseases. In addition, resveratrol has been e…

Cigarette smoking is a known cause of many cancers, yet epidemiologic studies have found protective associations with the risk of four "estrogen-related" malignancies: endometrial cancer, endometrioid and clear cell ovarian cancers, and thy…

Flavonoids are polyphenolic phytochemicals produced in fruits, nuts and vegetables and dietary consumption of these structurally diverse compounds is associated with multiple health benefits including increased lifespan, decreased cardiovas…

The nuclear receptor (NR) superfamily of transcription factors encodes expression of 48 human genes that are important for maintaining cellular homeostasis and in pathophysiology, and this has been observed for all sub-families including or…

The three-orphan nuclear receptor 4A genes are induced by diverse stressors and stimuli, and there is increasing evidence that NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor1) play an important role in maintaining cellular homeostasis and in …

Endometriosis is an inflammatory disease that primarily affects women during their reproductive years, and since current hormonal therapies are of concern, new hormone-independent treatment regimens are needed. The orphan nuclear receptor 4…

Endocrine-disrupting compounds (EDCs) are environmental contaminants that modulate estrogen, androgen, and thyroid hormone receptor signaling and it has been hypothesized that human exposures to EDCs induce multiple adverse health effects. …