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.

Most analyses of hemoglobin A1c (HbA1c) and multiple common diseases have focused on European populations, thus there is a need for Mendelian randomization phenome-wide association study (MR-PheWAS) in East Asian populations. We used MR-PheWAS to investigate the potential causal associations between HbA1c and 159 types of diseases in the Biobank Japan dataset, employing the inverse variance weighted as the primary statistical approach, supplemented by MR-Egger and weighted median analyses. Additionally, multiple sensitivity analyses were conducted to assess heterogeneity and pleiotropy. High HbA1c levels are associated with an increased risk of type 1 diabetes (odds ratio [OR] = 4.07; 95% confidence interval [CI]: 2.34~7.07), type 2 diabetes (OR = 4.76; 95% CI: 3.01~7.55), cataract (OR = 1.33; 95% CI: 1.18~1.51), diabetic nephropathy (OR = 5.70; 95% CI: 2.24~14.46), and peripheral arterial disease (OR = 1.62; 95% CI: 1.29~2.04). Conversely, elevated HbA1c levels are associated with a reduced risk of asthma (OR = 0.76; 95% CI: 0.67~0.86), breast cancer (OR = 0.75; 95% CI: 0.65~0.87), and cerebral aneurysm (OR = 0.71; 95% CI: 0.57~0.88). The results of the causal association between HbA1c and numerous diseases in East Asian populations provides insights for the region’s specialized glycemic control and disease prevention programs, as well as new preventive and treatment options.

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-β1) secretion, transcriptional repressor Snail expression, and β-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-β1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-β1 secretion, Snail mRNA level, and β-catenin protein expression. Moreover, activating β-catenin blocked the effects of ECAD on EMT, MET and TGF-β1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing β-catenin to inhibit TGFβ1 and its target genes, and finally facilitates airway epithelia repair.

Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.