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CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease

3 months 2 weeks ago
CHI3L1/YKL-40 is an astrocyte-secreted glycoprotein recognized as a biomarker of CNS inflammation and implicated in Alzheimer's disease (AD) cognitive decline. However, its precise pathological role remains unclear. Here, we investigate CHI3L1's function and its therapeutic potential in AD using both human induced pluripotent stem cell-derived neurogenesis models and in vivo conditional AD mouse models, with astrocyte-specific CHI3L1 knockout, alongside 5XFAD mice. Our data reveal that CHI3L1...
Xin Yang

Multiomic identification of senescent stem cell populations critical for osteoarthritis progression and therapy in subchondral bones

3 months 2 weeks ago
Osteoarthritis (OA) is a challenging degenerative joint disease with limited treatment options. Subchondral bone plays a critical role in maintaining joint homeostasis and influencing OA progression. Here, we investigated the role of senescence in mesenchyme-derived stem/progenitor cells (MDSPCs) during OA progression, aiming to identify potential therapeutic targets. Histopathological evaluations and bioinformatic analyses of OA samples from both humans and mice revealed that EGFR^(+) MDSPCs...
Pei Lin Li

Effectiveness of mindfulness-based interventions on inflammaging: a systematic review and meta-analysis

3 months 2 weeks ago
Mindfulness cultivates awareness, presence, and non-judgmental acceptance, enhancing overall well-being. Inflammaging, linking age and aged-related diseases, manifests through heightened levels of IL-6, TNF-α, and CRP, impacting aging indicators like TA, TL, PWV, and FMD. To assess how mindfulness-based interventions (MBIs) affect inflammaging, a search was conducted in PubMed, Web of Science, Cochrane Central Register, and ProQuest Dissertation & Theses Global up to March 2024. Criteria...
Xiaohong Huang

Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review

3 months 2 weeks ago
The intensive production and use of plastics, poor biodegradability and inadequate recycling have caused excessive and alarming environmental pollution. This has led to the inevitable intake by humans, through different routes, of small plastic particles, the micro and nano-plastics (MNPs) with sizes ranging from nanometers (<1000 nm) to micrometers (from 5 mm to 1 µm). MNPs can cause harmful effects in human tissues and organs, contributing to the early onset of aging and various age-related...
Carmela Rita Balistreri

AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial

3 months 2 weeks ago
Alzheimer's Disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, we demonstrate that our robust and interpretable AI-guided tool (predictive prognostic model, PPM) enhances precision in patient stratification, improving outcomes and decreasing sample size for a AD clinical trial. The AMARANTH trial of lanabecestat, a BACE1 inhibitor, was deemed futile, as treatment did not change cognitive outcomes, despite...
Delshad Vaghari

Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes

3 months 2 weeks ago
Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules. These...
Preman J Singh