Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats DOI Creative Commons
Thomas W. Jackson, John S. House, Andres R. Henriquez

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 21, 2023

Abstract Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of target tissue and effects are poorly understood. A prototypic inducer stress, ozone causes respiratory multiorgan through activation a neuroendocrine stress response. The goal this study was assess transcriptomic signatures multiple tissues serum metabolomics understand how adrenal-derived hormones contribute health outcomes. Male Wistar Kyoto rats (12–13 weeks old) were exposed filtered air or 0.8 ppm for 4-hours, blood/tissues collected immediately post-exposure. Each had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 hypothalamus, 2,516 adrenals, 1,333 liver, 1,242 adipose, 5,102 muscle (adjusted p-value < .1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, which 447 significantly altered ozone-exposed fold change 20%). total 6 differentially expressed all tissues. Glucocorticoid signaling, hypoxia, GPCR signaling commonly changed, but induced tissue-specific changes oxidative immune processes, metabolic pathways. Genes upregulated by TNF-mediated NFkB tissues, those defining inflammatory response tissue-specific. Upstream predictor common mediators including glucocorticoids, although specific responsible these predictors varied tissue. Metabolomic showed major lipids, amino acids, metabolites gut microbiome, concordant with transcriptional pathway within muscle, adipose distribution receptors ozone-induced involve induction unique gene networks phenotypes, shared initiating triggers converge into pathway-level responses. This multi-tissue analysis, combined circulating assessment, allows characterization inhaled pollutant-induced

Language: Английский

MiR-29a efficiently suppresses the generation of reactive oxygen species and α-synuclein in a cellular model of Parkinson's disease by potentially targeting GSK-3β DOI Creative Commons
Ya‐Ling Yang, Tsu‐Kung Lin, Ying‐Hsien Huang

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 974, P. 176615 - 176615

Published: April 27, 2024

MicroRNA-29a (miR-29a) has been suggested to serve a potential protective function against Parkinson's disease (PD); however, the exact molecular mechanisms remain elusive. This study explored role of miR-29a in cellular model PD using SH-SY5Y cell lines through iTRAQ-based quantitative proteomic and biochemistry analysis. The findings showed that mimic cells treated with 1-methyl-4-phenylpyridinium (MPP+) significantly decreased death increased mitochondrial membrane potential. It also reduced reactive oxygen species (ROS) production α-synuclein. Subsequent heatmap analysis proteomics revealed remarkably contrasting protein expression profiles for 882 genes when comparing groups plus MPP + control group solely MPP+. KEGG pathway these indicated substantial (P = 1.58x10

Language: Английский

Citations

0
Metal ion-complexed DNA probe coupled with CRISPR/Cas12a amplification and AuNPs for sensitive colorimetric assay of metallothionein in fish DOI
Wenjiao Zhou,

Yu Xiang,

Jirong Yang

et al.

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2024, Volume and Issue: 321, P. 124682 - 124682

Published: June 21, 2024

Language: Английский

Citations

0
Interpretable machine learning classifiers implicate GPC6 in Parkinson’s disease from single-nuclei midbrain transcriptomes DOI Creative Commons
Sali M.K. Farhan,

Michael R. Fiorini,

Jialun Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Parkinson’s disease (PD) is a progressive and devastating neurodegenerative disease. An incomplete understanding of its genetic architecture remains major barrier to the clinical translation targeted therapeutics, necessitating novel approaches uncover elusive determinants. Single-cell single-nuclear RNA sequencing (scnRNAseq) can help bridge this gap by profiling individual cells for disease-associated differential gene expression nominating genes genomic analyses. Here, we introduce machine learning framework identify molecular features that characterize post-mortem brain from PD patients. We train classifiers distinguish between healthy cells, then decode models unravel ‘reasons’ behind classifications, revealing key signatures parkinsonian brain. Application three publicly available snRNAseq datasets characterizing midbrain identified cell-type-specific sets accurately classify across all datasets, demonstrating our approach's capacity robust markers Targeted analyses revealed previously undescribed association rare variants in GPC6, member heparan sulfate proteoglycan family, which have been implicated intracellular accumulation α-synuclein preformed fibrils. replicate separate case-control cohorts. Our method promises enhance complex diseases like PD, representing critical step toward therapeutics. readily applicable diseases.

Language: Английский

Citations

0
Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats DOI Creative Commons
Thomas W. Jackson, John S. House, Andres R. Henriquez

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 21, 2023

Abstract Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of target tissue and effects are poorly understood. A prototypic inducer stress, ozone causes respiratory multiorgan through activation a neuroendocrine stress response. The goal this study was assess transcriptomic signatures multiple tissues serum metabolomics understand how adrenal-derived hormones contribute health outcomes. Male Wistar Kyoto rats (12–13 weeks old) were exposed filtered air or 0.8 ppm for 4-hours, blood/tissues collected immediately post-exposure. Each had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 hypothalamus, 2,516 adrenals, 1,333 liver, 1,242 adipose, 5,102 muscle (adjusted p-value < .1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, which 447 significantly altered ozone-exposed fold change 20%). total 6 differentially expressed all tissues. Glucocorticoid signaling, hypoxia, GPCR signaling commonly changed, but induced tissue-specific changes oxidative immune processes, metabolic pathways. Genes upregulated by TNF-mediated NFkB tissues, those defining inflammatory response tissue-specific. Upstream predictor common mediators including glucocorticoids, although specific responsible these predictors varied tissue. Metabolomic showed major lipids, amino acids, metabolites gut microbiome, concordant with transcriptional pathway within muscle, adipose distribution receptors ozone-induced involve induction unique gene networks phenotypes, shared initiating triggers converge into pathway-level responses. This multi-tissue analysis, combined circulating assessment, allows characterization inhaled pollutant-induced

Language: Английский

Citations

0