Background Spinal Cord Injury ( SCI ) is a disease leading to permanent neurological dysfunction. In recent years, exosomes and non-coding RNAs have been considered as potential therapeutic agents for spinal cord injury. Based on ceRNA regulatory network, the role of non-coding RNAs has been paid attention to, and some genes related to the pathological process after spinal cord injury have been found. However, most gene studies only focus on exosomes and non-coding RNAs in spinal cord injury sites, and few genes related to spinal cord injury repair have been found. Objective We aimed to identify exosomes and non-coding RNA in peripheral blood after spinal cord injury, and to predict its role in spinal cord injury according to gene expression profiles. Materials and methods After successful modeling of spinal cord injury, rat exosomes were extracted from peripheral blood.Western-Blot was used to identify exosomes. After RNA was extracted from exosomes, total transcriptome sequencing and differential gene GO and KEGG Pathway analysis were performed. We selected potential genes for quantitative Real-Time PCR (qRT-PCR) assays and predicted their potential regulatory networks. Results The successful establishment of spinal cord injury model was confirmed by Tarlov’s scores, and the extracted exosomes were confirmed by Western-Blot and electron microscopy. Among the significantly differentially expressed lncRNAs, XR_351404, XR_353833, XR_590719, XR_590076, and XR_591455 were associated with miRNA related to repair after spinal cord injury. Conclusions The regulatory effect of this network may play a key role in the repair process of SCI. The differential lncRNAs we found may serve as therapeutic targets and diagnostic biomarkers for SCI.
BackgroundAround one‐third of people with dementia worldwide might be attributable to seven modifiable risk factors, implying that interventions to control these risk factors may delay the onset of dementia. Therefore, we initiated the multimodal interventions to delay dementia and disability in rural China (MIND‐China) in 2018 and updated the main progresses of the project in 2018‐2021.MethodsMIND‐China is designed as a community‐based 2‐year cluster‐randomized, controlled, multimodal intervention study, which targets people who are aged 60‐79 years and living in the rural communities of Yanlou Town, western Shandong Province, China. Following the baseline examination in 2018, 52 villages in Yanlou Town are randomly (cluster‐randomization) divided into three groups: control group (regular primary health care service), vascular intervention group, and multimodal intervention group. The vascular intervention includes healthy lifestyle guidelines and the national guidelines‐based medical treatment of major cardiometabolic risk factors. The multimodal intervention group receives, in addition to the interventions planned for vascular intervention, group physical exercise, personalized leisure activities, and cognitive training.ResultsIn March‐September 2018, 5,765 participants underwent the core module assessments via face‐to‐face interviews, clinical examinations, neuropsychological testings, and laboratory tests (74.9% of all eligible residents). The mean age was 70.9 years (SD 5.9), 57.2% were women, 40.6% were illiterate, and 88.3% were farmers. Specific modules of examination were performed for subsamples (e.g., brain MRI scans, genetic and blood biomarkers, physical function, sleep quality, audiometric testing, and OCT examination). In May‐September 2019, the pilot study was completed to test the feasibility of the intervention programs and the implementation procedure in 7 villages (2 villages in control group, 3 villages in vascular intervention group, and 2 villages in multimodal intervention group). Recruitment of participants for interventions started in October 2019. In July‐November 2021, we conducted the 1‐year follow‐up assessments of participants in the interventions.ConclusionBy the end of 2021, MIND‐China had completed baseline screening assessment, recruitment of intervention participants, and the first follow‐up assessments following the initiation of interventions. MIND‐China demonstrates the feasibility of implementing the multimodal interventions in rural communities. COVID‐19 has minimal impact so far on the project.
Background Early-life educational attainment represents a major proxy for cognitive reserve (CR) that could benefit late-life cognitive function. We sought to investigate the associations of lifelong CR capacity with dementia and mild cognitive impairment (MCI) among people with limited education, while paying special attention to subtypes of dementia and MCI. Methods This population-based cohort study included 2127 participants (age ≥ 60 years; 59.4% women; 81.5% illiteracy or elementary school) who were free of dementia at baseline (August-December 2014) and undertook follow-up examinations in March-September 2018. Lifelong CR at baseline was estimated by integrating early-life education, adulthood occupation and marital status, and late-life physical activity, social activity, and social support using the structural equation models. Dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) were diagnosed following the international criteria. MCI and amnestic and non-amnestic MCI were defined following the Petersen’s criteria. Data were analyzed using Cox proportional-hazards models. Results During the total of 8330.63 person-years of follow-up, 101 were diagnosed with dementia, including 74 with AD and 26 with VaD. Medium and high (vs. low) tertiles of lifelong CR score were associated with multi-adjusted hazards ratio (95% confidence interval, CI) of 0.63 (0.40–1.00) and 0.27 (0.14–0.54) for dementia and 0.60 (0.35–1.02) and 0.18 (0.07–0.49) for AD. The association between higher CR and reduced AD risk was significant in young-old (60–74 years) but not in old-old people (≥ 75 years) (Pinteraction=0.011). Similarly, medium and high (vs. low) CR levels were associated with multi-adjusted hazard ratio (95% CI) of 0.81 (0.62–1.05) and 0.54 (0.40–0.73) for MCI and 0.73 (0.54–0.98) and 0.50 (0.36–0.70) for amnestic MCI. Lifelong CR was not significantly related to VaD or non-amnestic MCI. There was no statistical interaction of lifelong CR with sex and APOE genotype on incident dementia or MCI. Conclusions High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. The association of high CR with reduced AD risk existed only in young-old people. This study highlights the importance of lifelong CR in in maintaining late-life cognitive health even among people with limited education.
Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with AD and 26 with VaD. The high (versus low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratio (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged≥75 years (P-for-interaction=0.011). Similarly, among MCI-free people at baseline (n=1635), the high (versus low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratio of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in in maintaining late-life cognitive health even among people with no or limited education.
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