Neuron-derived exosome from plasma show altered miRNA cargo as a function of antidepressant drug response.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE148576 | GEO | 2021/10/28
REPOSITORIES: GEO
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Project description:The loss of muscle size, strength and quality with ageing, is a major determinant of morbidity and mortality in the elderly. The regulatory pathways that impact on the muscle phenotype include the translational regulation maintained by microRNAs (miRNA). Yet the miRNAs that are expressed in human skeletal muscle and whose expression levels correlate to muscle size, strength and quality are unknown. Here we used next-generation sequencing to characterise the expression profile of miRNAs in the m. vastus lateralis obtained by biopsy from middle-aged males (n=48; 50.0±4.3 years). Isokinetic strength testing and mid-thigh computed tomography was undertaken for muscle phenotype analysis. miR-486-5p accounted for 21% of the total miR sequence reads, with miR-10b-5p, miR-133a-3p, and miR-22-3p accounting for a further 15%, 12% and 10% respectively. Isokinetic knee extension strength and muscle cross-sectional area were positively correlated with miR-100-5p, miR-99b-5p and miR-191-5p expression. Whilst muscle attenuation, reflective of myofiber lipid content was negatively correlated to let-7f-5p, miR-30d-5p and miR-125b-5p expression. In-silico analysis implicates miRNAs related to strength and muscle size in the regulation of mammalian target of rapamycin, whist miRNAs related to muscle attenuation may have potential roles controlling the transforming growth factor- β/SMAD3 pathway which regulated fibrosis, adipogenesis and lipid accumulation.
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Project description:Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16). Small-RNA-seq of RNA-pEVs was performed to identify differentially regulated small-RNAs (sRNAs) in EoE.Basal vs. controls and EoE.Basal vs. EoE.Post.tx comparisons. Candidate miRNAs were validated in an independent cohort (EoE patients, n=33; controls, n=14), and the diagnostic potential of miRNAs-pairs was assessed. Results: the pEVs-sRNA cargo differed among controls, EoE.Basal and EoE.Post.tx conditions. Compared with controls, Ser_Comb_22, Leu_Comb_5, miR-10b-5p and miR-125a-5 were upregulated in EoE.Basal, and miR-224-5p, miR-221-3p, let-7d-5p and miR-191-5p were downregulated. Combination of miR-221-3p and miR-10b-5p showed the best diagnostic performance in discovery (AUC=0.87) and validation (AUC=0.70) cohorts. Comparing EoE.Basal and EoE.Post.tx paired samples, miR-374a-5p and miR-30a-3p were upregulated in EoE.Basal, while miR-15a-5p and let-7d-5p were downregulated. Here, combination of mi-30a-3p and miR-15a-5p showed AUC values of 0.90 and 0.71 in discovery and validation cohorts respectively. MiR-30a-3p remained highly upregulated in EoE.Basal when compared to EoE.Post.tx in the validation cohort (p=0.001). Conclusions: The sRNA cargo of pEVs is related to the inflammatory activity in EoE. This study pioneers the use of pEVs as a non-invasive biomarker for EoE.
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