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Blood-brain barrier-penetrative lipid nanoparticles enable systemic delivery of TRIM11 mRNA to disaggregate Tau in Alzheimer's disease models

2 weeks 2 days ago
Hyperphosphorylated Tau aggregates are a central pathological hallmark of Alzheimer's disease (AD), yet no approved therapy directly targets this process. mRNA therapeutics provide a transient and non-viral option but are limited by the blood-brain barrier (BBB). TRIM11 is an ATP-independent disaggregase that dissolves pathological Tau fibrils and promotes proteasomal clearance. Here, a ligand-free lipid nanoparticle (PLNP) is developed with zwitterionic, acetylcholine-mimetic...
Yan Zou

TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas

2 weeks 2 days ago
Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and...
Youri Hoogstrate

The aging cornea: From mechanisms to clinical applications

2 weeks 2 days ago
Aging is a multifactorial process characterized by a gradual decline in function, increased susceptibility to diseases, and diminished regenerative capacity. As the primary refractive structure and barrier of the eye, the cornea undergoes significant structural and functional changes during aging, making individuals more prone to various ocular surface diseases. Key age-related corneal changes include epithelial thinning, stromal remodeling with increased collagen cross-linking, endothelial cell...
Xueer Zheng

Exercise training improves mitochondrial oxidative energy metabolism through PGC-1α-dependent transcriptional pathway in the aged rat heart

2 weeks 2 days ago
Exercise training improves the age-induced decline in oxidative metabolic capacity in cardiac mitochondria. Nuclear respiratory factor-1 (NRF-1) signaling via peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates genes encoding mitochondrial oxidative metabolic enzymes. However, the effects of aging and subsequent exercise training on fatty acid (FA) metabolism-related gene expression via the myocardial PGC-1α-NRF-1 pathway, and the relevance of these changes to...
Kotaro Nakao

Aging Triggers an Intestinal Energy Crisis and HDL3 Deficiency Disrupting Gut-Liver Axis Homeostasis

2 weeks 2 days ago
During aging, decreased intestinal barrier function and its ability to synthesize metabolites are closely associated with various age-related diseases. However, the mechanism by which impaired intestinal synthesis contributes to gut-liver axis aging remains unclear. This study reveals that aging induces a mitochondrial energy crisis and defective membrane localization of ABCA1, significantly inhibiting the biosynthesis of high-density lipoprotein 3 (HDL3) in the intestine. Exogenous...
Yumeng Li

Amyloid-β as a target to suppress tonic PTH hypersecretion in hyperparathyroidism due to vitamin D deficiency

2 weeks 2 days ago
Hyperparathyroidism is an endocrine disorder linked to vitamin D deficiency. Reduced vitamin D receptor (VDR) activity promotes parathyroid hormone (PTH) hypersecretion by increasing heterodimerization of the type B γ-aminobutyric acid receptor 1 (GABA(B1)R) with the extracellular Ca^(2+)-sensing receptor (CaSR) in parathyroid cells; however, endogenous activators of the heterodimers are unknown. We uncovered increased expression of amyloid-β peptide cleaved from the amyloid-β precursor protein...
Chia-Ling Tu