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APOE4, the major genetic risk factor for Alzheimer's disease (AD), and ATP-binding cassette-A1 (ABCA1), required for lipidation of APOE are gene products of the liver X receptor (LXR) receptor. LXR agonists have been validated in animal models as therapeutics for AD, atherosclerosis, and many other diseases. Clinical progress has been thwarted by unwanted hepatic lipogenesis. Structurally diverse LXR ligands were profiled in coregulator TR-FRET (CRT) assays analyzing ligand-induced coactivator...

The accumulation of aberrant proteins or their impaired clearance leads to neurodegenerative diseases (NDs). The protein amino terminus (Nt) and its modifications determine the fate of proteins and their cellular effects. Nt acetylation, Nt methylation, and Nt myristoylation are protein Nt modifications implicated in the pathogenesis of proteinopathies like Alzheimer's, Parkinson's, and Huntington's diseases by regulating the protein lifespan, folding, and interaction with protein/DNA. In...

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) represent a promising cell-free strategy for intervertebral disc degeneration (IDD). Here, we obtained oxidative stress-preconditioned exosomes (O-Exos) from BMSCs exposed to low-concentration hydrogen peroxide. Compared with exosomes from untreated cells (N-Exos), O-Exos more effectively delayed nucleus pulposus (NP) cell senescence and attenuated IDD in vitro and in vivo. The superior effects of O-Exos were associated with...

Aging-related metabolic dysregulation and vascular vulnerability contribute substantially to stroke susceptibility, yet subtype-specific metabolic signatures remain incompletely characterized. Employing a nested case-control design within the Taizhou Longitudinal Study, we quantified 296 lipoprotein parameters and 54 metabolites in 1208 stroke-control pairs using nuclear magnetic resonance. Logistic regression estimated subtype-specific associations, and machine learning constructed prediction...

Resting heart rate (RHR) is an accessible measure that may reflect age-related cardiovascular and autonomic dysregulation relevant to cognitive ageing. However, evidence linking RHR with cognitive outcomes is inconsistent, and most studies relied on single baseline measurements that may not capture cumulative exposure. This study examined the associations of baseline and longitudinally averaged RHR with cognitive decline and dementia in older adults. This was a secondary analysis of the ASPirin...

Two dangerous viruses are back in the spotlight, reminding health officials how quickly infectious diseases can become serious threats. Hantavirus, often linked to rodents, can cause severe heart and lung complications and has no specific treatment or vaccine, while certain strains can even spread between people. Ebola remains one of the world's most feared diseases, with some outbreaks killing up to half of those infected, although vaccines and antivirals have improved outcomes for some strains.

New call for proposals seeks alternatives, though critics say the agency’s original choice is still leading option

Chemical signature of 3I/ATLAS suggests it formed early in the history of the Milky Way