Project description:We conducted this study to determine whether exosome regulation underlies the antimigraine mechanisms of acupuncture. By comparing serum samples from patients with migraine and healthy controls using high-throughput small RNA sequencing technology , we identified 705 exosomal microRNAs that are differentially expressed in patients with migraine, and this set of 705 microRNAs included five that are particularly well characterised (hsa-miR-369-5p, hsa-miR-1268b, hsa-miR-145-5p, hsa-miR-222-5p, and hsa-miR-4488). By comparing serum samples collected from patients with migraine before and after acupuncture treatment, we showed that acupuncture normalised the expression levels of those five well-characterised exosomal microRNAs.
Project description:Background:CircRNAs are non-coding RNA molecules that have recently been described and shown to regulate miRNA functionality. While recent studies have suggested such circRNAs to be associated with pain related diseases in humans, no comprehensive migraine-related circRNA profiles have been generated and there is currently no clear understanding of whether they can serve as regulators of migraine pathology. Methods:We initially conducted a circRNA microarray analysis of the plasma of migraine patients and healthy controls. Based upon these data, we then selected 8 differentially expressed circRNAs and confirmed their expression in more migraine patient plasma samples via real-time PCR. We then performed functional and pathway enrichment analyses. Lastly, using a robust rank aggregation approach, we constructed a ceRNA network according to predicted circRNA–miRNA and miRNA–mRNA pairs in these migraine patient samples. Results:we were able to detect 2039 circRNAs in our patient samples, with and 794 of 1245 these circRNAs being up- and down-regulated in migraine patients relative to controls, respectively (fold change ≥1.5, P < 0.01). A qRT-PCR analysis confirmed that the expression of hsa_circRNA_100236, hsa_circRNA_102413, and hsa_circRNA_000367 was significantly enhanced in migraine patients, whereas the expression of hsa_circRNA_103809, hsa_circRNA_103670, and hsa_circRNA_101833 was significantly reduced in these individuals relative to healthy controls. We found these differentially regulated circRNAs to be associated with numerous predicted biological processes, with enrichment analyses suggesting that they may modulate PI3K-Akt signaling so as to promote inflammation to drive migraine development. However, further research will be needed to formally test these mechanistic possibilities and to validate these circRNAs as potential biomarkers of migraine patients.Conclusions: our results offer new potential insights into the mechanistic basis of this condition, and suggest that hsa_circRNA_000367 and hsa_circRNA_102413 may offer value as regulators of migraine pathology.
Project description:The identification of the genetic risk factors in patients with isolated cleft palate by whole genome sequencing analysis. Pathogenic or likely pathogenic variants were discovered in genes associated with CP (TBX22, COL2A1, FBN1, PCGF2, and KMT2D) in five patients; hence, rare disease variants were identified in 17% of patients with non-syndromic isolated CP. Our results are relevant to routine genetic counselling practice and genetic testing recommendations.
Project description:Background: Migraine is a prevalent neurological disorder that affects a significant portion of the global population. Previous studies have suggested that microRNAs (miRNAs) may play a crucial role in the pathogenesis of migraine. This study aims to explore the potential functions of miRNAs through sequencing analysis of the Sp5C in a migraine mouse model. Method: Migraine mouse models were established through repeated inflammatory soup dural injections. Total RNA was extracted from the Sp5C of both the migraine and control groups. High-throughput sequencing technology was employed to analyze the miRNA expression profiles, followed by differential expression analysis using bioinformatics tools. Pathway enrichment analysis was performed based on differential expressed miRNAs, and literature review was conducted to identify target genes for subsequent animal experiments. Results: Compared to the control group, we identified four miRNAs with differential expression (fold change ≥1.5, P < 0.05), all of which were upregulated in the migraine model group. These miRNAs included miR-12179-5p, miR-23b-5p, miR-214-5p, and miR-6239. We employed online miRNA prediction tools (Targetscan, miRWalk, and miRDB) and obtained 7,909 predicted target genes. Bioinformatics analysis of these target genes identified several enriched signaling pathways, with particular interest in chemotaxis, immune receptor activity, immune system development, and the MAPK signaling pathway. These pathways play important roles in mediating pain and neuroinflammation. Based on a literature review and bioinformatics analysis, we identified Cxcr5 as a potential key gene for further research. Conclusion: Our results indicated that four upregulated miRNAs (miR-12179-5p, miR-23b-5p, miR-214-5p, and miR-6239) were identified in the migraine model compared to the control group. Whether Cxcr5 can serve as a key regulatory gene for migraine treatment requires further experimental validation.
Project description:Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump alpha2-Na/K ATPase represent a key genetic cause of familial hemiplegic migraine, but the mechanisms by which alpha2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we unexpectedly find that mice in which alpha2-Na/K ATPase is conditionally deleted in astrocytes display episodic transient motor paralysis. Functional neuroimaging reveals that conditional knockout of alpha2-Na/K ATPase triggers spontaneous cortical spreading depression events that are associated with low voltage activity events upon EEG monitoring, which in turn correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that loss of alpha2-Na/K ATPase alters metabolic gene expression in astrocytes in vivo with consequent elevation of serine and glycine in the brain. Strikingly, feeding alpha2-Na/K ATPase knockout mice a serine- and glycine-free diet reverses the phenotype of transient motor impairment. Together, our findings define a novel metabolic mechanism regulated by astrocytic alpha2-Na/K ATPase that triggers episodic transient motor paralysis in mice, laying the foundation for potential new treatment strategies for patients with familial hemiplegic migraine.
2020-10-20 | GSE145102 | GEO
Project description:Gut microbiota in patients with migraine
| PRJNA1120654 | ENA
Project description:Genetic variants of patients with Wilson's disease
Project description:Migraine is primarily mediated via CGRP signaling on various tissues to induce pain and other migraine symptoms. We characterize the role of migraine related CGRP signaling on meningeal lymphatic vessels from mouse meningeal lymphatic tissue. In this dataset, we include the expression data obtained from lyve-1 positive meningeal lymphatic endothelial cells from Lyve-1 cre mediated HA-tagged ribosomes from mice with the NTG mediated model of migraine. These data are used to obtain 700 genes that are differentially expressed in meningeal lymphatic tissue in response to NTG induced migraine.
2024-05-08 | GSE266558 | GEO
Project description:Whole exome sequencing identified novel variants in five CHARGE syndrome patients
| PRJNA604965 | ENA
Project description:Genetic variants of patients with hereditary spastic paraplegia