Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis

Abstract Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks. Methods Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit. Results We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks. Conclusions It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation.

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Characterization of MicroRNA and Gene Expression Profiles Following Ricin Intoxication

Toxins ◽

10.3390/toxins11050250 ◽

2019 ◽

Vol 11 (5) ◽

pp. 250 ◽

Cited By ~ 4

Author(s):

Nir Pillar ◽

Danielle Haguel ◽

Meitar Grad ◽

Guy Shapira ◽

Liron Yoffe ◽

...

Keyword(s):

Gene Expression ◽

Mirna Expression ◽

Mononuclear Cells ◽

Immune Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Specific Pattern ◽

Peripheral Blood Mononuclear ◽

Pulmonary Exposure ◽

Mirna Expression Profiles

Ricin, derived from the castor bean plant, is a highly potent toxin, classified as a potential bioterror agent. Current methods for early detection of ricin poisoning are limited in selectivity. MicroRNAs (miRNAs), which are naturally occurring, negative gene expression regulators, are known for their tissue specific pattern of expression and their stability in tissues and blood. While various approaches for ricin detection have been investigated, miRNAs remain underexplored. We evaluated the effect of pulmonary exposure to ricin on miRNA expression profiles in mouse lungs and peripheral blood mononuclear cells (PBMCs). Significant changes in lung tissue miRNA expression levels were detected following ricin intoxication, specifically regarding miRNAs known to be involved in innate immunity pathways. Transcriptome analysis of the same lung tissues revealed activation of several immune regulation pathways and immune cell recruitment. Our work contributes to the understanding of the role of miRNAs and gene expression in ricin intoxication.

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Expression Profiling of Transcriptome and Its Associated Disease Risk in Yang Deficiency Constitution of Healthy Subjects

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/1493098 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Ruoxi Yu ◽

Yin Yang ◽

Yuanyuan Han ◽

Pengwei Hou ◽

Yingshuai Li ◽

...

Keyword(s):

Gene Expression ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Clinical Medicine ◽

Disease Risk ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Evidence ◽

Chinese Han ◽

Peripheral Blood Mononuclear

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of “constitution-disease correlation” in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n=20) and balanced constitution (n=8) (aged 18–28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of “constitution-disease correlation.”

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