Targeting vascular dementia: Molecular docking and dynamics of natural ligands against neuroprotective proteins

by Zhizhong Wang, Sen Xu, Ailong Lin, Chunxian Wei, Zhiyong Li, Yingchun Chen, Bizhou Bie, Ling Liu

Vascular dementia (VaD), a neurodegenerative disease driven by vascular pathology, requires multi-targeted therapeutic strategies. This study employs an integrated in silico approach to evaluate the neuroprotective potential of natural ligands against key proteins implicated in VaD pathogenesis. Using molecular docking and normal mode analysis (NMA), four natural compounds (Galangin, Resveratrol, Curcumin, and Licocumarone) were assessed for their binding affinity and structural influence on six target proteins: APLP1, APOE, CLDN5, SOD1, MMP9, and MTHFR. Docking analysis revealed that galangin exhibited the highest binding affinity to APLP1 (−8.5 kcal/mol), resveratrol to MTHFR (−8.1 kcal/mol), and curcumin showed dual efficacy toward APOE (−7.2 kcal/mol) and MMP9 (−8.0 kcal/mol). Licocumarone demonstrated notable stabilization of CLDN5 and SOD1. The NMA results indicated ligand-induced stabilization of protein cores and enhanced flexibility in loop regions, which may impact amyloid aggregation, oxidative stress, and blood-brain barrier integrity. Pathway enrichment using the KEGG and Reactome databases identified significant involvement of the IL-17 and TNF signaling pathways, along with leukocyte transendothelial migration, linking inflammation with vascular dysfunction. APOE emerged as a central node within the protein-protein interaction network, highlighting its regulatory importance. This study highlights the therapeutic relevance of natural ligands as cost-effective modulators of multiple VaD-associated pathways. The combined use of molecular docking, protein dynamics, and enrichment analyses provides a comprehensive computational framework for early-stage drug discovery. These findings warrant further experimental validation to advance the development of targeted, mechanism-driven interventions for vascular dementia.

A Systematic Review and Meta‐Analysis of the Effects of Couple‐Based Dyadic Intervention on the Psychological Distress of Cancer Patients and Their Partners

ABSTRACT

Aims and Objective

To explore the effectiveness of dyadic intervention on the psychological distress of cancer patients and their partners.

Background

Cancer patients and their partners demonstrated high levels of psychological distress. However, the effects of dyadic intervention on psychological distress were unclear.

Design

A systematic review and meta-analysis of randomised controlled trials was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.

Methods

A systematic search on couple-based dyadic intervention for cancer patients and their partners was carried out across eight databases. Our review adhered to the Cochrane risk-of-bias tool as its foundational framework, and data extraction and analysis followed standardised checklists for quantitative research studies.

Results

No statistically significant effects were reported on patients' anxiety, depressive symptoms, or cancer-related distress. However, subgroup analysis revealed that interventions lasting 6 or 12 weeks had positive effects on patients' cancer-related distress. Significant reductions in cancer-related distress scores were only observed when interventions included communication and support (CS) and skill building (SB) components, however. Additionally, patients experienced higher distress levels with less than six interventions or session durations shorter than 6 h. For partners, couple-based dyadic interventions significantly reduced their anxiety and depressive symptom levels.

Conclusions

Couple-based dyadic interventions, with either 6- or 12-week durations, or encompassing both CS and SB components, demonstrated significantly positive effectiveness on patients' psychological distress. Couple-based dyadic interventions also exhibited a propensity for alleviating psychological distress in both cancer patients and their partners, with a more pronounced impact observed among partners.

Relevance to Clinical Practice

This meta-analysis highlights the effectiveness of dyadic interventions in reducing psychological distress in cancer patients and their partners. Healthcare professionals should incorporate these interventions into their care practices.

No Patient or Public Contribution

Direct contributions from patients or the public were not included in this review.

Trial Registration

PROSPERO number: CRD42023418978; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=418978