Episodic memory network characteristics in patients with amnestic mild cognitive impairment accompanied by executive function impairment.

OBJECTIVE: To explore the functional connectivity (FC) characteristics of the episodic memory network (EMN) in amnestic mild cognitive impairment (aMCI) patients with different levels of executive function (EF). METHODS: This study included 76 participants from the Alzheimer's Disease Neuroimaging Initiative database, comprising 23 healthy controls (HCs) and 53 aMCI patients. Based on EF levels, aMCI patients were categorized into aMCI-highEF and aMCI-lowEF groups. Cognitive function scores, pathological markers (cerebrospinal fluid ß-amyloid, total tau protein, phosphorylated tau protein, AV45-PET, and FDG-PET), and functional magnetic resonance imaging were collected and compared among the three groups. Seed-based FC analysis was used to examine differences in the EMN among the groups, and partial correlation analysis was employed to investigate the relationship between changes in FC and cognitive function scores as well as pathological markers. RESULTS: Compared to the aMCI-highEF group, the aMCI-lowEF group exhibited more severe cognitive impairment, decreased cerebral glucose metabolism, and elevated AV45 levels. Significant FC differences in the left superior temporal gyrus (STG) of the EMN were observed among the three groups. Post hoc analysis revealed that the aMCI-lowEF group had increased FC in the left STG compared to the HCs and aMCI-highEF groups, with statistically significant differences. Correlation analysis showed a significant negative correlation between the differences in FC in the left STG of aMCI-highEF and aMCI-lowEF groups and Rey Auditory Verbal Learning Test forgetting scores. Receiver operator characteristic curve analysis indicated an area under the curve of 0.741 for distinguishing between aMCI-highEF and aMCI-lowEF groups based on FC of left STG, with a sensitivity of 0.808 and a specificity of 0.667. CONCLUSION: aMCI-lowEF exhibits characteristic changes in FC within the EMN, providing theoretical support for the role of EF in mediating EMN alterations and, consequently, impacting episodic memory function.

Cfa-circ002203 was upregulated in rapidly paced atria of dogs and involved in the mechanisms of atrial fibrosis.

Background and aims: The role of circular RNAs (circRNAs) in the pathophysiology of cardiovascular disease is gradually being elucidated; however, their roles in atrial fibrillation (AF)-related fibrosis are largely unknown. This study aimed to characterize the different circRNA profiles in the rapid-pacing atria of dogs and explore the mechanisms involved in atrial fibrosis. Methods: A rapid right atrial-pacing model was established using electrical stimulation from a pacemaker. After 14 days, atrial tissue was collected for circRNA sequencing analysis. In vitro fibrosis was established by stimulating canine atrial fibroblasts with angiotensin II (Ang II). The fibroblasts were transfected with siRNA and overexpressing plasmids to explore the effects of cfa-circ002203 on fibroblast proliferation, migration, differentiation, and the expression of fibrosis-related proteins. Results: In total, 146 differentially expressed circRNAs were screened, of which 106 were upregulated and 40 were downregulated. qRT-PCR analysis showed that cfa-circ002203 was upregulated in both in vivo and in vitro fibroblast fibrosis models. The upregulation of cfa-circ002203 enhanced proliferation and migration while weakening the apoptosis of fibroblasts. Western blotting showed that cfa-circ002203 overexpression increased the protein expression levels of fibrosis-related indicators (Col I, Col III, MMP2, MMP9, and α-SMA) and decreased the protein expression levels of pro-apoptotic factors (Bax and Caspase 3) in Ang II-induced fibroblast fibrosis. Conclusion: Cfa-circ002203 might serve as an active promoter of the proliferation, migration, and fibrosis of atrial fibroblasts and is involved in AF-induced fibroblast fibrosis.

Screening and functional analysis of differentially expressed lncRNAs in rapid atrial pacing dog atrial tissue.

PURPOSE: Atrial fibrillation (AF) is one of the most commonly sustained arrhythmias in clinical practice. Long non-coding RNAs (lncRNAs) are gene regulatory elements involved in the development of several diseases. We aimed to explore the expression characteristics of lncRNAs associated with AF. METHODS: We randomly assigned 12 adult healthy mongrel dogs into a control group and an atrial pacing group. Atrial pacing stimulation was performed at a high frequency of 500 beats per min for 14 consecutive days in the atrial pacing group. HE and Masson staining were used to detect rapid atrial pacing induced atrial fibrosis. Total RNA extraction was performed on dog atrial tissues and was used for high-throughput sequencing of lncRNAs. RESULTS: A total of 10,310 lncRNAs were detected, and 33 differentially expressed lncRNAs were screened. Among them, 19 lncRNAs were upregulated in the atrial pacing group, and 14 lncRNAs were downregulated. Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and interaction networks showed that AF-related lncRNAs participate in the regulation of AF in diverse biological processes, cellular components, molecular functions, signaling pathways, and complex interactions with miRNAs and mRNAs. Five differentially expressed lncRNAs were selected for RT-PCR validation, and the verification results were consistent with the results of lncRNA sequencing. CONCLUSIONS: In summary, our study enhances our understanding of the biological functions of AF-related lncRNAs by screening and analyzing differentially expressed lncRNAs, and the results help to enrich the theoretical basis for the treatment of atrial fibrillation.