scholarly journals Peripheral Blood Mononuclear Cell Proteome Changes in Patients with Myelodysplastic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Klara Pecankova ◽  
Pavel Majek ◽  
Jaroslav Cermak ◽  
Jan E. Dyr

Our aim was to search for proteome changes in peripheral blood mononuclear cells (PBMCs) of MDS patients with refractory cytopenia with multilineage dysplasia. PBMCs were isolated from a total of 12 blood samples using a Histopaque-1077 solution. The proteins were fractioned, separated by 2D SDS-PAGE (pI 4–7), and double-stained. The proteomes were compared and statistically processed with Progenesis SameSpots; then proteins were identified by nano-LC-MS/MS. Protein functional association and expression profiles were analyzed using the EnrichNet application and Progenesis SameSpots hierarchical clustering software, respectively. By comparing the cytosolic, membrane, and nuclear fractions of the two groups, 178 significantly (P<0.05, ANOVA) differing spots were found, corresponding to 139 unique proteins. Data mining of the Reactome and KEGG databases using EnrichNet highlighted the possible involvement of the identified protein alterations in apoptosis, proteasome protein degradation, heat shock protein action, and signal transduction. Western blot analysis revealed underexpression of vinculin and advanced fragmentation of fermitin-3 in MDS patients. To the best of our knowledge, this is the first time that proteome changes have been identified in the mononuclear cells of MDS patients. Vinculin and fermitin-3, the proteins involved in cell adhesion and integrin signaling, have been shown to be dysregulated in MDS.

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.


Epigenomics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 439-454 ◽  
Author(s):  
Fangpu Yu ◽  
Yuanyuan Tie ◽  
Ya Zhang ◽  
Zunzhe Wang ◽  
Liwen Yu ◽  
...  

Aim: We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary heart disease (CHD). Materials & methods: We performed sequence analysis of circRNAs in peripheral blood mononuclear cells of 70 CHD patients and 30 controls. Eight selected circRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in human atherosclerotic coronary arteries. Results: In total, 2283 downregulated and 85 upregulated circRNAs were identified in CHD. Parental genes of top 100 dysregulated-circRNAs are related to metabolism and protein modification, and 12 circRNAs might upregulate their CHD-related parental genes through miRNA sponges. Of the eight circRNAs validated in atherosclerotic coronary arteries by qRT-PCR, six were consistent with sequencing results of peripheral blood mononuclear cells. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in CHD pathophysiology.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2932 ◽  
Author(s):  
Stine M. Ulven ◽  
Kirsten B. Holven ◽  
Amanda Rundblad ◽  
Mari C. W. Myhrstad ◽  
Lena Leder ◽  
...  

A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.


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