scholarly journals Assessment of miR-181b-5p, miR-23a-3p, BCL-2, and IL-6 in Peripheral Blood Mononuclear Cells of Autistic Patients; Likelihood of Reliable Biomarkers

2020 ◽  
Author(s):  
Hossein Atwan ◽  
Mohammad-Ali Assarehzadegan ◽  
Mehdi Shekarabi ◽  
Seyed Mohammad Jazayeri ◽  
Shahram Barfi ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rna Extraction ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
The Other ◽  
Peripheral Blood Mononuclear ◽  
Other Hand ◽  
Blood Mononuclear Cells

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible.  

scholarly journals Comparison of procedures for RNA-extraction from peripheral blood mononuclear cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0229423
Author(s):  
Antonio Rodríguez ◽  
Hans Duyvejonck ◽  
Jonas D. Van Belleghem ◽  
Tessa Gryp ◽  
Leen Van Simaey ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rna Extraction ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals A new strategy to uncover fragile X proteomic biomarkers using the nascent proteome of peripheral blood mononuclear cells (PBMCs)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Olivier Dionne ◽  
François Corbin
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Rna Binding ◽  
Mononuclear Cells ◽  
Fragile X ◽  
Enrichment Analysis ◽  
Autism Spectrum ◽  
Label Free ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractFragile X syndrome (FXS) is the most prevalent inherited cause of intellectual disabilities and autism spectrum disorders. FXS result from the loss of expression of the FMRP protein, an RNA-binding protein that regulates the expression of key synaptic effectors. FXS is also characterized by a wide array of behavioural, cognitive and metabolic impairments. The severity and penetrance of those comorbidities are extremely variable, meaning that a considerable phenotypic heterogeneity is found among fragile X individuals. Unfortunately, clinicians currently have no tools at their disposal to assay a patient prognosis upon diagnosis. Since the absence of FMRP was repeatedly associated with an aberrant protein synthesis, we decided to study the nascent proteome in order to screen for potential proteomic biomarkers of FXS. We used a BONCAT (Biorthogonal Non-canonical Amino Acids Tagging) method coupled to label-free mass spectrometry to purify and quantify nascent proteins of peripheral blood mononuclear cells (PBMCs) from 7 fragile X male patients and 7 age-matched controls. The proteomic analysis identified several proteins which were either up or downregulated in PBMCs from FXS individuals. Eleven of those proteins were considered as potential biomarkers, of which 5 were further validated by Western blot. The gene ontology enrichment analysis highlighted molecular pathways that may contribute to FXS physiopathology. Our results suggest that the nascent proteome of PBMCs is well suited for the discovery of FXS biomarkers.

scholarly journals A New Strategy to Uncover Fragile X Proteomic Biomarkers Using the Nascent Proteome of Peripheral Blood Mononuclear Cells (PBMCs)

2021 ◽  
Author(s):  
Olivier Dionne ◽  
François Corbin
Keyword(s):  
Western Blot ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Rna Binding ◽  
Mononuclear Cells ◽  
Fragile X ◽  
Autism Spectrum ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Potential Biomarkers

Abstract Background: Fragile X syndrome (FXS) is the most prevalent inherited cause of intellectual disabilities and autism spectrum disorders. FXS result from the loss of expression of the FMRP protein, an RNA binding protein that regulate the expression of key synaptic effectors. FXS is also characterized by a wide array of behavioral, cognitive and metabolic impairments. The severity and penetrance of those comorbidities are extremely variable, meaning that a considerable phenotypic heterogeneity is found among fragile X individuals. Unfortunately, clinicians currently have no tools at their disposal to assay patient’s prognosis upon diagnosis. Since the absence of FMRP was repeatedly associated with an aberrant translational metabolism, we decided to study the nascent proteome in order to screen for potential proteomic biomarkers of FXS.Method: We used a BONCAT (Bioothogonal Non-canonical Amino Acids Tagging) method coupled to label-free mass spectrometry to purify and quantify nascent proteins of peripheral blood mononuclear cells from 7 fragile X male patients that do not express FMRP and 7 age-matched controls. Candidate biomarkers were confirmed by Western blot. Results: The proteomic analysis identified several proteins which were either up or downregulated in absence of FMRP in FXS individuals as compared to controls. Eleven of those proteins were considered as potential biomarkers, from which 5 were further validated by Western blot. The gene ontology enrichment analysis highlighted molecular pathway that may contribute to FXS physiopathology. Conclusions: Our results showed that the nascent proteome is well suited for the discovery of FXS biomarkers. In fact, taking advantage of a key alteration in FXS physiopathology led us to successfully identified 11 potential biomarkers.

Sign in / Sign up

Export Citation Format

Share Document