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.

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.

Methylation of host genes is promising for the triage of women with high-risk human papillomavirus (HR-HPV) infections. This study aimed to validate the potential value of Glycophorin C (GYPC) methylation (GYPCm) in the early detection of cervical cancer. We recruited HR-HPV-positive women at the hospital outpatient clinic between August and December 2023, using cytology triage. The remaining exfoliated cervical cells were subjected to GYPCm testing. A total of 549 cases were finally included for analysis: 156 cervicitis, 303 cervical intraepithelial neoplasia (CIN)1, 49 CIN2, 37 CIN3, and 4 CC. The difference of GYPCm ΔCp values between CIN1 and CIN2 was statistically significant in the pathology results of 549 participants (P < 0.001). The optimal threshold value of GYPCm for detecting CIN2 + was 6.35. The GYPCm adjusted ORs for CIN2 + and CIN3 + were 31.23 (95%CI: 16.53–58.99) and 34.68 (95%CI: 11.90–101.11), respectively. In all individuals, the sensitivity of GYPCm for CIN2 + and CIN3 + was consistent with that of cytology (CIN2 + 83.3%; CIN3 + 90.2%), with higher specificity than that of cytology (CIN2 + 85.8 vs. 29.4%; CIN3 + 79.7 vs. 28.7%, all P < 0.001). The sensitivity and negative predictive value (NPV) of HPV16/18 combined GYPCm for CIN3 + were not statistically different from those of HPV combined with cytology (sensitivity 95.1 vs. 97.6%, P = 0.317; NPV 99.4 vs. 99.0%, P = 0.613). The net reclassification improvement for HPV16/18 combined GYPCm and its combined cytology to classify CIN2 + vs. < CIN2 was 48.8% (95%CI: 39.7–57.9%, P < 0.001), with a relative colposcopy referral rate of 50.1% (95%CI: 45.5–54.7%). GYPCm has a higher CIN2 + OR and higher specificity and positive predictive value than cytology in HR-HPV-positive women and is a potential molecular biomarker for triaging HR-HPV (+) to detect cervical (pre)cancer.

Objective: To investigate the role and molecular mechanism of the GATA2/ZNF486/JAM2 transcriptional regulatory axis in the invasion and migration of Uterine Corpus Endometrial Carcinoma (UCEC). Methods: We employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) to assess the expression levels of ZNF486, GATA2, and JAM2 in UCEC cell lines. Lentivirus-mediated overexpression and knockdown cell lines were established, and CCK-8, colony formation, Transwell, and wound healing assays were performed to evaluate cell proliferation, invasion, and migration. WB and immunofluorescence were used to detect changes in epithelial-mesenchymal transition (EMT) markers. The direct binding and transcriptional activation of target gene promoters by transcription factors were confirmed through ChIP-qPCR and dual-luciferase reporter assays. Results: ZNF486 was significantly downregulated in UCEC. Its overexpression upregulated E-cadherin, downregulated N-cadherin and Vimentin, and markedly inhibited cell proliferation, invasion, and migration. Mechanistically, ZNF486 directly bound to and transcriptionally activated the JAM2 promoter; knockdown of JAM2 partially attenuated the tumor-suppressive effects of ZNF486. Furthermore, GATA2 was identified as an upstream transcription factor that directly activated ZNF486 transcription; knockdown of ZNF486 abrogated the tumor-suppressive effects induced by GATA2 overexpression. Conclusion: GATA2 inhibits EMT, invasion, and migration in UCEC by transcriptionally activating the ZNF486-JAM2 axis. This pathway provides a potential molecular framework for understanding UCEC progression.

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.

Endometrial cancer (EC) is one of the most common gynaecological malignancies worldwide [1,2], with an increasing incidence partly attributed to rising obesity rates and an aging population [3]. Ea...