Dataset Information

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.

SUBMITTER: Aczel T

PROVIDER: S-EPMC8493693 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveThis post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE-2 study.BackgroundEptinezumab, a monoclonal antibody that inhibits calcitonin gene-related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE-2 patients diagnosed with both CM and MOH.MethodsThe phase 3, double-blind, placebo-controlled PROMISE-2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders-3β criteria. This post hoc analysis evaluated changes in total and class-specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM.ResultsIn PROMISE-2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1-24, as well as 6.3% (6/96) of patients who received placebo.ConclusionsAcross 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one-fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period.

Project description:BackgroundZiziphora bungeana Juz. is a folk medicine from the Xinjiang Uygur Autonomous Region. The herb or the aerial parts of it have been used to medicinally treat cardiovascular diseases. Flavonoids are the main pharmacologically active ingredients in Z. bungeana. Identification of the tissue-specific distribution of flavonoids in Z. bungeana is crucial for effective and sustainable medicinal use of the plant. Furthermore, understanding of the biosynthesis pathways of these flavonoids in Z. bungeana is of great biological significance.MethodsThe flavonoids from different tissues of Z. bungeana were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The full-length transcriptome of Z. bungeana was determined using a strategy based on a combination of Illumina and PacBio sequencing techniques. The functions of differentially expressed unigenes were predicted using bioinformatics methods and further investigated by real-time quantitative PCR and phylogenetic relationship analysis.ResultsAmong the 12 major flavonoid components identified from Z. bungeana extracts, linarin was the most abundant component. Nine flavonoids were identified as characteristic components of specific tissues. Transcriptome profiling and bioinformatic analysis revealed that 18 genes were putatively involved in flavonoid biosynthesis. The gene expression and phylogenetic analysis results indicated that ZbPALs, Zb4CL3, ZbCHS1, and ZbCHI1 may be involved in the biosynthesis of the main flavonoid intermediate. ZbFNSII, ZbANS, and ZbFLS may be involved in the biosynthesis of flavones, anthocyanins, and flavonols, respectively. A map of the biosynthesis pathways of the 12 major flavonoids in Z. bungeana is proposed.ConclusionsThe chemical constituent analysis revealed the compositions of 9 characteristic flavonoids in different tissues of Z. bungeana. Linarin can be hydrolysed into acacetin to exert a pharmaceutical role. Apigenin-7-O-rutinoside is hypothesised to be the precursor of linarin in Z. bungeana. There was greater content of linarin in the aerial parts of the plant than in the whole herb, which provides a theoretical basis for using the aerial parts of Z. bungeana for medicine. These results provide a valuable reference for further research on the flavonoid biosynthesis pathways of Z. bungeana and will be significant for the effective utilisation and ecological protection of Z. bungeana.