Aging closely correlates with impaired cognitive abilities, including learning, attention, and memory. These impairments are typically linked to disturbances in dopaminergic signaling and hippocampus theta oscillations, two essential processes involved in memory encoding and novelty detection. This review examines the relationship between theta oscillation activity and dopaminergic novelty detection processes, offering a fresh framework for improving adult cognitive function through virtual reality (VR)-based methods. The specific purpose of this review is to investigate how dopaminergic novelty detection and theta oscillations can be leveraged through VR-based adaptive interventions to enhance cognitive function in aging populations. It investigates how exposure to new stimuli in a VR setting may activate dopaminergic neurons and induce synchronized theta rhythms to improve memory and learning. The potential for adaptive VR systems that adjust task difficulty and novelty based on real-time neural feedback is also clarified by this review. By combining results from behavioral, electrophysiological, and neuroimaging research, it supports the development of tailored, non-invasive therapies that focus on the neurological underpinnings of cognitive decline. This approach is promising for reducing age-related cognitive decline and enhancing cognitive resilience throughout life.

Exercise has profound positive effects on cognitive function and brain health throughout different life stages. This systematic review aims to evaluate the multifaceted impacts of exercise on cognitive function, neuroplasticity, neurotransmitter expression, cerebrovascular function, and age-related cognitive decline across the lifespan. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched PubMed, Web of Science, and Scopus databases for studies examining exercise interventions and cognitive function. Eligibility criteria included studies involving human participants across all age groups and animal models focusing on molecular mechanisms. The review employed qualitative synthesis to examine exercise modalities and age-specific effects. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists. A total of 37 studies were included in the final synthesis (young adults: 2, middle-aged adults: 7, older adults/neurodegenerative diseases: 13, molecular mechanisms: 15). Regular physical activity, including aerobic, resistance, and combined training, significantly enhances cognitive abilities, promotes neuroplasticity, and mitigates age-related cognitive decline. Key molecular mechanisms include upregulation of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and modulation of dopaminergic and serotonergic systems. Exercise serves as a potent non-pharmacological intervention for maintaining cognitive vitality and mental health. Limitations include heterogeneity in exercise protocols and outcome measures across studies. Future research should focus on multi-omics approaches to further elucidate cell-type-specific effects.

Neurodevelopment is a highly ordered, precisely regulated process that establishes the neurobiological foundations of cognition, thought, emotion, and behavior. Neurodevelopmental disorders (NDDs) display marked phenotypic and genetic heterogeneity and variably impair learning, daily functioning, and social adaptation. As a key epigenetic mechanism, histone lysine methylation shapes chromatin accessibility and transcriptional programs, exerting central roles in neural stem cell fate decisions, neuronal migration and circuit assembly, as well as synaptic plasticity and learning and memory. Focusing on the activating histone H3 lysine 4 (H3K4) methylation marks (H3K4me1/2/3), this review synthesizes evidence for the bidirectional regulation mediated by “writers” (the KMT2/SET/DOT1) and “erasers” (the KDM/LSD and KDM5) in NDDs, including Kabuki syndrome, Wiedemann-Steiner syndrome, autism spectrum disorder, and schizophrenia. We further outline how animal models, patient-derived brain organoids, and multi-omics atlases enhance mechanistic insight, and we discuss the translational potential of small-molecule interventions, and metabolic modulation. Together, we summarize how the precise balance of methylation writing and erasure—and its crosstalk with DNA methylation and histone acetylation—forms an epigenetic network that drives neurodevelopmental programs. Targeting this network offers testable therapeutic avenues for NDDs.

Berberine (BBR) exerts an effective protection for diabetic retinopathy (DR), but the underlying key molecular mechanism remains unknown; this study investigated the protective mechanism of BBR on DR by alleviating cell pyroptosis. A rat DR model was established and treated with BBR, and histological analyses, including hematoxylin and eosin staining, Nissl staining, and immunofluorescence, were executed to evaluate tissue changes. Core target genes were identified using the GeneCards database, Venn diagram analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction networks, and molecular docking. Validation of key genes was performed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and RNA interference. BBR improved retinal morphology, reduced edema, and restored the arrangement of retinal ganglion cells in DR rats. BBR significantly reduced the levels of pyroptosis markers such as IL-1β and IL-18, which were elevated in DR. Network pharmacology identified 10 hub genes, with six genes (JUN, STAT3, AKT1, TP53, IL-1B, EGFR) further analyzed. BBR reversed DR-induced upregulation of JUN, STAT3, and AKT1 at both the mRNA and protein levels, as confirmed by RT-qPCR and Western blot. Silencing these genes enhanced cell viability and amplified BBR's protective effects. Altogether, BBR alleviates retinal inflammation and pyroptosis in diabetic retinal ganglion cells by targeting JUN, STAT3, and AKT1, providing insights into its therapeutic potential for DR.

Accumulating epidemiological and mechanistic evidence indicates that anti-inflammatory dietary patterns may attenuate systematic inflammation underlying chronic disease, including epilepsy (EP), a common and potentially debilitating neurological disorder frequently complicated by sleep disturbances. Herein, we aim to assess the inflammatory potential of habitual diets among individuals with EP, and co-occurring sleep disorders (SLDs). From 2013 to March 2020, 35,706 participants were enrolled in this study. EP status was defined based on reported use of antiepileptic drugs within the preceding 30 days. SLDs were assessed using questions on habitual sleep duration and validated self-reported sleep disturbances. Dietary inflammatory index (DII) and energy-adjusted DII (E-DII) scores were calculated using 24-h dietary recall data. Individuals with EP exhibited significantly higher DII and E-DII scores and a greater prevalence of SLDs compared with individuals without EP. In the fully adjusted model, participants in Quartile 4 of the DII score had significantly increased odds of EP and SLDs, relative to those in Quartile 1. Mediation analyses revealed that DII accounted for 2.650% to 6.234% of the association between EP and SLDs. In stratified analysis, an elevated prevalence of SLDs was observed across Quartile 2–4 for DII and in Quartile 2 and 4 for E-DII among individuals with EP. Individuals with EP consume diets with greater pro-inflammatory potential than those without EP. SLDs in this population are associated with higher dietary inflammatory burden—highlighting the need for evidence-informed, individualized nutritional guidance as part of comprehensive EP management.

Hemorrhagic stroke (HS) remains a serious and potentially disabling complication following heart valve replacement (HVR). We aimed to evaluate the incidence and predictors of HS among mechanical HVR patients in Bangladesh. The Multidimensional Approach of Genotype and Phenotype In Stroke Etiology (MAGPIE) is an ambispective study recruited 568 consecutive HVR patients who had long-term (≥6 months) warfarin therapy between January 2010 and December 2024. Among the 568 HVR patients, 4.4% experienced HS, with a mortality rate of 52%, and the median age was 40 years (interquartile range [IQR]: 32–45). The median duration of warfarin uses among mechanical heart valve patients with HS varied by procedure: 63 months (IQR: 48–86) for mitral valve replacement, 60 months (12–85) for aortic valve replacement, 96 months (52–101.50) for double valve replacement, and 42 months (24–60) for patients undergoing coronary artery bypass grafting (CABG) with valve replacement. Additionally, a receiver operating characteristic curve analysis identified 104 months as the discriminatory threshold for warfarin therapy duration in predicting post-HVR HS onset. An age- and sex-adjusted logistic regression model identified severe pulmonary hypertension (odds ratio [OR] 4.44; 95% confidence interval [CI] 1.15–17.04; p = 0.02) and warfarin therapy duration ≥104 months (OR 1.99; 95% CI 1.00–3.76; p = 0.04) as independent predictors of HS in patients with mechanical HVR. Severe pulmonary hypertension was associated with a 4.4-fold higher risk and warfarin therapy beyond 104 months with a twofold higher risk of HS among patients with mechanical HVR.

Flavone derivatives of natural products are often synthesized to enhance their structural specificity, target selectivity, and bioavailability. The current study aimed to examine the neuroprotective efficacy of flavone derivative in diabetic associated neurodegenerations through systematic assessments of in-silico and in-vivo. The synthesized flavone (2-phenyl-4H-chromen-4-one) was characterized by NMR spectroscopy and FTIR. The in-vivo assessments were performed by following the serum biochemistry of homeostatic model assessment (HOMA), antioxidant and histopathology of cortex and hippocampus. The in-silico assessment of molecular docking showed −6.6 Kcal/mol with dipeptidyl peptidase-4 enzyme (DPP4), −7.8 with acetylcholinesterase (AChE), and −9.5 with butyrylcholinesterase (BuChE). The diabetic neurodegeneration model was induced by the chemical induction method and treated with the test compound at a dose of 40 mg/kg in comparison to sitagliptin. The treatment of the test compound showed significant alterations in the cortex and hippocampus region with mitigated neuronal injuries which endorsed by expressions targeted genes including glucose transporter 3 (GLUT-3), glycogen synthase kinase 3 beta (GSK-3β), microtubule associated protein (MAP)-Tau, and peroxisome proliferator-activated receptor gamma (PPARγ). Furthermore, the lipid profile and oxidative stress were ameliorated significantly by the course of treatment. In conclusion, the synthesized flavone has significant capability to promote neuroprotective effects in diabetes associated neurodegeneration through mitigating oxidative stress and modulating the expression of the targeted genes, thereby alleviating neuronal injuries.