Apelin-13, a neuropeptide, has been recognized for its neuroprotective properties. Our previous study found apelin-13 improves cognitive function in Alzheimer’s disease (AD) rats by inhibiting neuroinflammation through upregulation of BDNF/TrkB signaling pathway. However, the precise mechanism by which apelin-13 modulates BDNF remains unclear. Thus, this study aimed to unravel the specific regulatory mechanism by which apelin-13 regulates BDNF. Bilaterally intracerebroventricular injection with Aβ25–35 was used to establish an in vivo model of AD. For the generation of METTL3 KO rats, the Crispr/Cas9 method was applied. PC12 cells were treated with Aβ25–35 to establish an in vitro model of AD. The cognitive function of the rats was evaluated with the Morris water maze and the novel object recognition test. Hippocampal damage and neuron loss were detected through H&E and immunofluorescent staining. METTL3, BDNF, TrkB, and p-TrkB were examined by Western blotting. Inflammation-related cytokines, IBA1, GFAP, IL-1β, and TNF-α were detected by Western blotting, immunofluorescent staining, ELISA, and qRT-PCR. m6A modification level was evaluated through MeRIP. A flow cytometer was applied to evaluate cell apoptosis. Cell proliferation was examined using MTT. m6A methylation inhibitor DAA reverses the improvement effect of apelin-13 on cognitive function, hippocampal nerve damage, neuron loss, and neuroinflammation in Aβ25–35-treated rats. Further results showed that apelin-13 upregulated METTL3, BDNF-AS m6A methylation, inhibited BDNF-AS expression, and subsequently upregulated BDNF/TrkB signaling pathway and reduced neuroinflammation in in vivo and in vitro AD models in a dose-dependent manner. Knockdown of METTL3 abolished apelin-13’s improvement effect in AD rats. Apelin-13-mediated upregulation of METTL3 enhances neuroinflammation inhibition and BDNF/TrkB signaling pathway via m6A-dependent downregulation of lncRNA BDNF-AS, thus ameliorating AD. Our study offers novel insights into the pathogenesis of AD and identifies potential drug targets for its treatment.

Background: Depression in cervical cancer (CC) patients concurrently compromises disease management and quality of life. However, significant discrepancies persist among existing studies regarding the determinants of depression in this population worldwide. To address this gap, this study employs meta-analysis to systematically identify and synthesize the contributing factors to depression among cervical cancer patients. Aim: To provide evidence-based references for mitigating depression risk among cervical cancer patients. Methods: Literature was searched in databases including CNKI, Wanfang, VIP, CBM, Web of Science, PubMed, and EMBASE from their inception until March 2025. The literature was screened, selected, quality assessed, and data extracted and analyzed. Meta-analysis was conducted using Revman 5.4 and Stata 18 software, with odds ratios (OR) and their 95% confidence intervals (CI) as the observed indicators. Results: A total of 1,108 articles were retrieved, with 15 articles ultimately included in the analysis. The results indicate that low educational attainment (OR = 3.25, 95% CI: 2.02–5.22), age ≥45 years (OR = 1.67, 95% CI: 1.09–2.55), inter-household monthly income disparity (OR = 3.06, 95% CI: 1.87–5.00), advanced tumor stage (OR = 1.99, 95% CI: 1.28–3.11), low social support (OR = 2.48, 95% CI: 1.95–3.16), moderate to severe pain (OR = 2.86, 95% CI: 1.76–4.65), limited disease awareness (OR = 2.58, 95% CI: 1.88–3.55), and undergoing hysterectomy (OR = 4.69, 95% CI: 3.03–7.24) are significant risk factors for depression in cervical cancer patients. Conclusion: The occurrence of depression in cervical cancer patients is influenced by multiple factors. Healthcare professionals and family members should conduct comprehensive assessments of patients' conditions to implement targeted prevention and intervention measures, thereby enhancing the psychological wellbeing of patients. Systematic review registration: https://inplasy.com/ , identifier: INPLASY202560039.

Objective: To elucidate the molecular targets and mechanisms by which Acorus tatarinowii exerts therapeutic effects in major depressive disorder (MDD) using network pharmacology and molecular docking approaches. Methods: Bioactive compounds of Acorus tatarinowii were identified from comprehensive pharmacological databases. MDD-related targets were sourced from extensive genomic repositories. Overlapping targets were determined and subjected to network topology and protein–protein interaction (PPI) analyses to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal pertinent biological processes and signaling pathways. Molecular docking simulations validated the interactions between key bioactive compounds and core targets. Results: A total of 57 bioactive compounds were identified in Acorus tatarinowii, including apigenin, heterotropan, and isoelemicin. Integrative analysis revealed 700 compound-related targets and 2590 MDD-associated targets, with 150 intersecting targets. Network analyses pinpointed five core targets: TP53, STAT3, AKT1, PIK3CA, and PIK3R1. GO enrichment identified 858 significant biological processes, while KEGG pathway analysis highlighted 155 enriched pathways, notably the PI3K-Akt, cAMP, and MAPK signaling pathways. Molecular docking studies demonstrated strong binding affinities between key compounds and their respective targets. Conclusions: This study delineates the multifaceted polypharmacological mechanisms through which Acorus tatarinowii may confer protective effects against major depressive disorder, underscoring its potential as a promising therapeutic agent.

Thesium chinense Turcz., a traditional Chinese medicinal herb, is enriched with bioactive constituents such as flavonoids and polysaccharides, demonstrating multifaceted therapeutic properties including anti-inflammatory, antioxidant, and neuroprotective effects. This review systematically elucidates the regulatory mechanisms by which active components of Thesium chinense Turcz. modulate pathological processes in NDDs, such as neuroinflammation and oxidative stress. Furthermore, it synthesizes evidence of its neuroprotective efficacy across experimental models and evaluates its translational potential for clinical applications. By integrating preclinical findings and mechanistic insights, this work provides a robust theoretical foundation for advancing natural product-based therapeutics in the management of NDDs.

Alzheimer’s disease (AD) is characterized by amyloid- β (Aβ) deposition, tau pathology, synaptic injury, neuroinflammation, oxidative stress, and disrupted organellar homeostasis. Peroxisomes maintain lipid and redox balance through very-long-chain fatty acid (VLCFA) β -oxidation, plasmalogen biosynthesis, and reactive oxygen species (ROS) metabolism. This Review evaluates how peroxisomal alterations may modulate APP processing and Aβ clearance, tau kinase/phosphatase balance, neuroinflammation, oxidative stress, and peroxisome-mitochondria crosstalk. We distinguish human correlational evidence from intervention studies in AD models and mechanistic extrapolation from primary peroxisomal disorders. Current evidence supports a context-dependent vulnerability or amplifier model rather than a universal causal pathway. Peroxisome-targeted interventions remain investigational, and no validated biomarker currently identifies an AD subgroup for such treatment.