Carbene reactive metabolite explains the hepatotoxicity of the hot flashes drug fezolinetant: A DFT investigation.

Fezolinetant, the first-in-class hot flashes drug, was flagged in September 2024 by US-FDA for liver injury. It is alarming that an FDA-approved drug shows liver toxicity within a year. Fezolinetant's metabolic pathways and metabolites are not disclosed in the FDA label, clinical trial, or other literature reports.

Enhanced paracrine action of FGF21 in stromal cells delays thymic aging.

Age-related thymic involution precedes aging of all other organs in vertebrates and initiates the process of declining T cell diversity, which leads to eventual immune dysfunction. Whether FGF21, a liver-derived pro-longevity hormone that is also produced in thymic stroma, including by adipocytes, controls the mechanism of thymic demise is incompletely understood. Here, we demonstrate that elevation of FGF21 in thymic epithelial cells (TECs) and in adipocytes protects against thymic aging, whereas conditional hepatic overexpression did not impact thymic biology in aged mice.

Impairment of DET1 causes neurological defects and lethality in mice and humans.

COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian COP1 binds to DET1 and is a substrate adaptor for the CUL4A-DDB1-RBX1 RING E3 ligase. Transcription factor substrates, including c-Jun, ETV4, and ETV5, are targeted for proteasomal degradation to effect rapid transcriptional changes in response to cues such as growth factor deprivation.

Symposia Report of The Annual Biological Sciences Section Meeting of the Gerontological Society of America 2023, Tampa, Florida.

The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and non-genetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health.

Psychiatric comorbidity in patients with migraine: A standardized interview-based study.

Background: Comorbidity of various psychiatric conditions with migraine is common and important. A thorough analysis of mental conditions in migraine is essential to encourage the holistic care of such patients.

Aim: To assess psychiatric comorbidity in patients with migraine using a well-standardized clinical diagnostic tool.