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1.
Front Genet ; 13: 686739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601482

RESUMO

Objective: This study aimed to exploit cellular heterogeneity for revealing mechanisms and identifying therapeutic targets for Parkinson's disease (PD) via single-cell transcriptomics. Methods: Single-cell RNA sequencing (scRNA-seq) data on midbrain specimens from PD and healthy individuals were obtained from the GSE157783 dataset. After quality control and preprocessing, the principal component analysis (PCA) was presented. Cells were clustered with the Seurat package. Cell clusters were labeled by matching marker genes and annotations of the brain in the CellMarker database. The ligand-receptor networks were established, and the core cell cluster was selected. Biological functions of differentially expressed genes in core cell clusters were analyzed. Upregulated marker genes were identified between PD and healthy individuals, which were measured in 18 PD patients' and 18 healthy individuals' blood specimens through RT-qPCR and Western blotting. Results: The first nine PCs were determined, which can better represent the overall change. Five cell clusters were identified, including oligodendrocytes, astrocytes, neurons, microglial cells, and endothelial cells. Among them, endothelial cells were the core cell cluster in the ligand-receptor network. Marker genes of endothelial cells possessed various biological functions. Among them, five marker genes (ANGPT2, APOD, HSP90AA1, HSPA1A, and PDE1C) were upregulated in PD patients' than in healthy individuals' endothelial cells, which were confirmed in PD patients' than in healthy individuals' blood specimens. Conclusion: Our findings revealed that the cellular heterogeneity of PD and endothelial cells could play a major role in cell-to-cell communications. Five upregulated marker genes of endothelial cells could be underlying therapeutic targets of PD, which deserve more in-depth clinical research.

2.
Biomed Res Int ; 2021: 6644827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834070

RESUMO

OBJECTIVE: This study is aimed at understanding the molecular mechanisms and exploring potential therapeutic targets for atrial fibrillation (AF) by multiomics analysis. METHODS: Transcriptomics and methylation data of AF patients were retrieved from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially methylated sites between AF and normal samples were screened. Then, highly expressed and hypomethylated and lowly expressed and hypermethylated genes were identified for AF. Weighted gene coexpression network analysis (WGCNA) was presented to construct AF-related coexpression networks. 52 AF blood samples were used for whole exome sequence. The mutation was visualized by the maftools package in R. Key genes were validated in AF using independent datasets. RESULTS: DEGs were identified between AF and controls, which were enriched in neutrophil activation and regulation of actin cytoskeleton. RHOA, CCR2, CASP8, and SYNPO2L exhibited abnormal expression and methylation, which have been confirmed to be related to AF. PCDHA family genes had high methylation and low expression in AF. We constructed two AF-related coexpression modules. Single-nucleotide polymorphism (SNP) was the most common mutation type in AF, especially T > C. MUC4 was the most frequent mutation gene, followed by PHLDA1, AHNAK2, and MAML3. There was no statistical difference in expression of AHNAK2 and MAML3, for AF. PHLDA1 and MUC4 were confirmed to be abnormally expressed in AF. CONCLUSION: Our findings identified DEGs related to DNA methylation and mutation for AF, which may offer possible therapeutic targets and a new insight into the pathogenesis of AF from a multiomics perspective.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Epigênese Genética , Genômica , Terapia de Alvo Molecular , Idoso , Caderinas/genética , Caderinas/metabolismo , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Mutação/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
3.
Biomed Res Int ; 2021: 6616434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791366

RESUMO

OBJECTIVE: In this study, we aimed to identify critical genes and pathways for multiple brain regions in Parkinson's disease (PD) by weighted gene coexpression network analysis (WGCNA). METHODS: From the GEO database, differentially expressed genes (DEGs) were separately identified between the substantia nigra, putamen, prefrontal cortex area, and cingulate gyrus of PD and normal samples with the screening criteria of p value < 0.05 and ∣log2fold change (FC) | >0.585. Then, a coexpression network was presented by the WGCNA package. Gene modules related to PD were constructed. Then, PD-related DEGs were used for construction of PPI networks. Hub genes were determined by the cytoHubba plug-in. Functional enrichment analysis was then performed. RESULTS: DEGs were identified for the substantia nigra (17 upregulated and 52 downregulated genes), putamen (317 upregulated and 317 downregulated genes), prefrontal cortex area (39 upregulated and 72 downregulated genes), and cingulate gyrus (116 upregulated and 292 downregulated genes) of PD compared to normal samples. Gene modules were separately built for the four brain regions of PD. PPI networks revealed hub genes for the substantia nigra (SLC6A3, SLC18A2, and TH), putamen (BMP4 and SNAP25), prefrontal cortex area (SNAP25), and cingulate gyrus (CTGF, CDH1, and COL5A1) of PD. These DEGs in multiple brain regions were involved in distinct biological functions and pathways. GSEA showed that these DEGs were all significantly enriched in electron transport chain, proteasome degradation, and synaptic vesicle pathway. CONCLUSION: Our findings revealed critical genes and pathways for multiple brain regions in PD, which deepened the understanding of PD-related molecular mechanisms.


Assuntos
Encéfalo/metabolismo , Bases de Dados de Ácidos Nucleicos , Regulação para Baixo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Regulação para Cima , Encéfalo/patologia , Humanos , Doença de Parkinson/genética , Doença de Parkinson/patologia
4.
Phys Chem Chem Phys ; 14(7): 2501-7, 2012 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-22249858

RESUMO

Mid-infrared laser ablation of water-rich targets at the maximum of the 2.94 µm absorption band is a two-step process initiated by phase explosion followed by recoil pressure induced material ejection. Particulates and/or droplets ejected by this high temperature high pressure process can be ionized for mass spectrometry by charged droplets from an electrospray. In order to gauge the internal energy introduced in this laser ablation electrospray ionization (LAESI®) process, we apply the survival yield method and compare the results with electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). The results indicate that LAESI yields ions with internal energies indistinguishable from those produced by ESI. This finding is consistent with the recoil pressure induced ejection of low micrometre droplets that does not significantly change the internal energy of solute molecules.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Raios Infravermelhos , Íons/química , Lasers , Pressão , Temperatura , Vitamina B 12/química
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