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Uracil-induced replication stress drives mutations, genome instability, anti-cancer treatment efficacy, and resistance

2 months 2 weeks ago
Uracil incorporation into DNA, as a result of nucleotide pool imbalances or cytosine deamination (e.g., through APOBEC3A/3B), can result in replication stress and is the most common source of mutations in cancer and aging. Despite the critical role of uracil in genome instability, cancer development, and cancer therapy, only now is there emerging data on its impact on fundamental processes such as DNA replication and genome stability. Removal of uracil from DNA by base excision repair (BER) can...
Oliver Mortusewicz

Cross-regulation between the nervous system and type 2 immunity

2 months 2 weeks ago
Interactions between the nervous and immune systems are critical to healthy physiology and are altered in many human diseases. Many of the major players in type 2 immune responses, including type 2 lymphocytes and cytokines, mast cells, and immunoglobulin E, have been implicated in neuronal function and behavior. Conversely, neurons in both the central and peripheral nervous systems can affect type 2 immune responses and behaviors relevant to allergy, such as food avoidance. Defining this...
Nicholas M Mroz

Epilepsy and autophagy modulators: a therapeutic split

2 months 2 weeks ago
Epilepsy is a neurological disease characterized by repeated unprovoked seizure. Epilepsy is controlled by anti-epileptic drugs (AEDs); however, one third of epileptic patients have symptoms that are not controlled by AEDs in a condition called refractory epilepsy. Dysregulation of macroautophagy/autophagy is involved in the pathogenesis of epilepsy. Autophagy prevents the development and progression of epilepsy through regulating the balance between inhibitory and excitatory neurotransmitters....
Hayder M Al-Kuraishy

Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients

2 months 2 weeks ago
Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary...
Pauline Mury

Changes in Home Care Clients' Sensory Impairment Status and Its Association With Functioning Over 18 Months: A Longitudinal Register-Based Study

2 months 2 weeks ago
We investigated the changes in home care clients' vision and hearing over 18 months and examined the role of sensory impairments in maintaining their functioning. We used data from the Finnish Resident Assessment Instrument (RAI) database (n = 7013). Sensory impairment status was categorized by type (single or dual) and severity (mild or moderate/severe). The association between sensory impairment and functioning over 18 months was examined using binary logistic regression analysis with...
Tiina Pesonen

Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration

2 months 2 weeks ago
Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post-mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence....
Jonathan Plessis-Belair

The association between the number of teeth and frailty among older adults: a systematic review and meta-analysis

2 months 2 weeks ago
CONCLUSIONS: There is a significant association between tooth count and frailty, particularly in those with 20 or fewer teeth. Policymakers should prioritize oral health within aging populations by promoting early preventive care and education to mitigate frailty risk. Robust, large-scale studies are needed to guide evidence-based interventions and public health policy.
Xiao-Ming Zhang

Microglial TMEM119 binds to amyloid-beta to promote its clearance in an Abeta-depositing mouse model of Alzheimer's disease

2 months 3 weeks ago
The progression of Alzheimer's disease (AD) involves temporal dynamics of microglial activation. Restoring or maintaining microglial homeostasis has emerged as a promising therapeutic strategy to combat AD. Transmembrane protein 119 (TMEM119) is a homeostatic marker of microglia but has not been fully studied under AD pathological conditions. Here, we observed that amyloid-beta (Aβ) induced a decrease in TMEM119 expression in microglia, and TMEM119 deficiency increased AD progression in the...
Jing Liu

The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer's disease

2 months 3 weeks ago
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...
N S Aathira