Exercise Modifies the Transcriptional Regulatory Features of Monocytes in Alzheimer’s Patients: A Multi-Omics Integration Analysis Based on Single Cell Technology

Chen, Yisheng; Sun, Yaying; Luo, Zhiwen; Chen, Xiangjun; Wang, Yi; Qi, Beijie; Lin, Jinrong; Lin, Weiwei; Sun, Chenyu; Zhou, Yifan; Huang, Jiaoling; Xu, Yuzhen; Chen, Jiwu; Chen, Shiyi

doi:10.3389/fnagi.2022.881488

Cited by 25 publications

(21 citation statements)

References 62 publications

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“…Cellular integration, dimensionality reduction, clustering, and cellular annotation of scRNA-seq data from this mouse were performed using standard single-cell analysis procedures based on the “Seurat” package as previous researches ( Stuart et al, 2019 ; Chen et al, 2022b ). First, quality control of scRNA-seq data was based on cell quality filtering criteria from previous studies.…”

Section: Methodsmentioning

confidence: 99%

“…Cell-cell communication analysis was used to explore context-dependent crosstalk across endothelial cell subtypes and other cell types during diabetes development and to identify genes that alter important physiological processes in endothelial cells ( Chen et al, 2022b ). CellPhoneDB, a database that can calculate ligand and receptor interactions between cells, was used to perform cell-cell communication analyses ( Efremova et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Huang

Lin

Sun

et al. 2022

Front. Aging Neurosci.

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IntroductionEndothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development.MethodsSingle cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose.ResultsSeven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism.ConclusionEC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Huang

Lin

Sun

et al. 2022

Front. Aging Neurosci.

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“…Exploring the relationship between NPC and pyroptosis-associated genes (PAGs) could aid in the understanding of HNSCC. Basic medical research can benefit from bioinformatics as it can provide information at multiple levels and aspects about molecular mechanisms of disease ( Holtsträter et al, 2020 ; Lin et al, 2021 ; Chen et al, 2022 ; Luo et al, 2022 ; Sun et al, 2022 ; Yan et al, 2022 ). Biomarkers related to PAGs for NPC-related bioinformatics can provide effective treatment for HNSCC.…”

Section: Introductionmentioning

confidence: 99%

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes

et al. 2022

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This study aimed to understand the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and to develop and validate a prognostic model for HNSCC based on pyroptosis-associated genes (PAGs) in nasopharyngeal carcinoma. The Cancer Genome Atlas database was used to identify differentially expressed PAGs. These genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes functional annotation analyses and Gene Ontology analyses. The NLR family pyrin domain containing 1 (NLRP1) gene, charged multivesicular body protein 7 (CHMP7) gene, and cytochrome C (CYCS) gene were used to create a prognostic model for HNSCC. The results of the Kaplan-Meier (K-M) and Cox regression analyses indicated that the developed model served as an independent risk factor for HNSCC. According to the K-M analysis, the overall survival of high-risk patients was lower than that of low-risk patients. The hazard ratios corresponding to the risk scores determined using the multivariate and univariate Cox regression analyses were 1.646 (95% confidence interval (CI): 1.189–2.278) and 1.724 (95% CI: 1.294–2.298), respectively, and the area under the receiver operator characteristic curve was 0.621. The potential mechanisms associated with the functions of the identified genes were then identified, and the tumor microenvironment and levels of immune cell infiltration achieved were analyzed. The immune infiltration analysis revealed differences in the distribution of Th cells, tumor-infiltrating lymphocytes, regulatory T cells, follicular helper T cells, adipose-derived cells, interdigitating dendritic cells, CD8+ T cells, and B cells. However, validating bioinformatics analyses through biological experiments is still recommended. This study developed a prognostic model for HNSCC that included NLRP1, CHMP7, and CYCS.

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“…Therefore, the hypothesis that aerobic and intensive exercise may slow cognitive impairment in older people is widely supported. However, previous studies have tended to use only mammalian models or cell experiment [for example, Chen et al (2022a) found that exercise can affect the complications of AD by affecting the activity of monocytes, and they also found that exercise can affect the up-regulation of miR-215 expression, thus playing a role of cognitive protection ( Chen et al, 2022b )], large-scale epidemiological surveys are extremely limited and the mechanisms are also unclear ( Lamb et al, 2018 ; Lourenco et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Association between physical exercise, executive function, and cerebellar cortex: A cross-sectional study among the elderly in Chinese communities

Chen

et al. 2022

Front. Aging Neurosci.

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BackgroundPrevious studies have confirmed that physical exercise may be beneficial for brain health, but there is little data on this among older Chinese.ObjectiveThe purpose of this study was to explore the relationship between physical exercise and cognitive impairment, and to explore the possible mechanism by which physical exercise prevents cognitive decline.Materials and methods192 older adults with dementia, 610 older adults with mild cognitive impairment (MCI), and 2,218 healthy older adults were included in the study. Through standardized questionnaires, we obtained their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension and diabetes) and physical exercise information (such as whether they did physical exercise and the frequency of physical exercise, etc.). The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, while the Wechsler block diagram was used to assess their executive function. Moreover, 164 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included hippocampus, gray matter, and cerebellar cortex.ResultsBy using stepwise multiple logistics regression analysis, we found that physical exercise was associated with both MCI (p = 0.001*, OR = 0.689, 95%CI: 0.553–0.859) and dementia (p < 0.001*, OR = 0.501, 95%CI: 0.354–0.709), independent of gender, age, education, and other factors. The results of ROC curve showed that the area under the curve of physical exercise in predicting MCI and dementia was 0.551 (p < 0.001*, 95%CI: 0.525–0.577) and 0.628 (p = 0.001*, 95%CI: 0.585–0.671), respectively. The results of partial correlation analysis showed that physical exercise was associated with left cerebellar cortex (r = 0.163, p = 0.023), right cerebellar cortex (r = 0.175, p = 0.015) and Wechsler block diagram score (r = 0.235, p = 0.011). Moreover, the results of linear regression analysis mediation model showed that physical exercise may affect Wechsler block diagram score through influencing the thickness of right cerebellum cortex, and the latter may play a partial mediation effect (indirect B = 0.001, p = 0.045).ConclusionPhysical exercise might be a protective factor for mild cognitive impairment and dementia among the Chinese elderly, and there might be an association among physical exercise, executive function, and the thickness of the cerebellar cortex.

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Exercise Modifies the Transcriptional Regulatory Features of Monocytes in Alzheimer’s Patients: A Multi-Omics Integration Analysis Based on Single Cell Technology

Cited by 25 publications

References 62 publications

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes

Association between physical exercise, executive function, and cerebellar cortex: A cross-sectional study among the elderly in Chinese communities

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