Effect of β-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes’ Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property

2019 ◽  
Vol 16 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Mahsa Taeb ◽  
Abdollah Jafarzadeh ◽  
Seyed Shahabeddin Mortazavi-Jahromi ◽  
Nahid Zainodini ◽  
Mohammad Reza Mirzaei ◽  
...  

Objective: This research aimed to study the anti-aging and anti-inflammatory effects of low and high doses of the β-D-mannuronic (M2000) on gene expression of enzymes involved in oxidative stress (including SOD2, GST, GPX1, CAT, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy donors under in vitro conditions. Methods: The PBMCs were separated and the RNAs were then extracted and the cDNAs synthesized, and expression levels of the mentioned genes were detected by qRT-PCR. Results: Our results indicated that the high dose of this drug could significantly reduce the expression level of the SOD2 gene compared to the lipopolysaccharide (LPS) group (p < 0.0001). Moreover, it was found that the high dose of this drug could significantly decrease the expression level of the GST gene compared to the LPS group (p < 0.0001). However, no significant reductions were observed in expression levels of the CAT and GPX1 genes compared to the LPS group. Furthermore, our data revealed that the level of iNOS and MPO gene expression was significantly reduced, in both doses of M2000, respectively, compared to the LPS group (p < 0.0001). Conclusion: This research showed that M2000 as a novel NSAID with immunosuppressive properties could modify oxidative stress through lowering expression levels of the SOD2, GST, iNOS, and MPO genes compared to the healthy expression levels, with a probable reduction of the risk of developing inflammatory diseases related to age and aging.

Author(s):  
Michal Stuss ◽  
Monika Migdalska-Sęk ◽  
Ewa Brzezianska-Lasota ◽  
Marta Michalska-Kasiczak ◽  
Pawel Bazela ◽  
...  

The purpose of the study was to assess the expression of selected genes of the Wnt pathway: APC, AXIN1, CTNNB1, DKK1, GSK3β, KREMEN1, SFRP1, WNT1 in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their BMD (bone mineral density) and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into 4 groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (REL) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and WNT1. In addition, the REL of DKK1, APC, and GSK3β genes were slightly elevated vs. the calibrator. In contrast, CTNNB1 and AXIN1 presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (p<0.05) of particular genes. However, we have observed quite numerous interesting correlations between the expression of the studied genes and BMD, the presence of fractures, and laboratory parameters, both in the whole studied population as well as in selected groups. In conclusion, the high level of CTNNB1 expression maintains normal BMD and/or protects against fractures. It also appears that the changes in expression levels of the Wnt pathway genes in PBMCs reflect the expected changes in bone tissue.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Marketou ◽  
J Kontaraki ◽  
K Fragiadakis ◽  
J Konstantinou ◽  
S Maragkoudakis ◽  
...  

Abstract Purpose MicroRNAs (miRs) play a major role in protein regulation by post-transcriptional gene expression and cell to cell interaction. Recently, they have been emerged as important modulators in cardiovascular development and disease. Our aim was to determine whether cardiac related miRs such as miR-208b was differentially expressed in peripheral blood mononuclear cells from patients with acute myocarditis. We also evaluated their expression levels in peripheral blood mononuclear cells in relation with left ventricular global longitudinal peak strain (GLPS) in those patients. Methods We assessed the expression levels of miR-208b in 55 patients with acute myocarditis (48 men, mean age 33±10 years) and 22 healthy individuals (18 men, mean age 33±9 years). Blood samples were taken on admission and miR expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. All patients were also underwent an assessment with standard conventional transthoracic and a two-dimensional speckle tracking echocardiography. Results GLPS was significantly reduced in the group of myocarditis compared to healthy individuals (from −13.9±10.9% versus −22.2±6.7%, p&lt;0.05). Myocarditis patients showed significantly higher miR-208b (28.8±16.6 versus 6.40±1.1, p&lt;0.001) expression levels compared to control group. miR-208b gene expression levels at baseline revealed a significant negative correlation with GLPS on admission (r=−0.51, p&lt;0.05). This correlation was independent of the patients' clinical parameters. Conclusions Our data reveal that miR-208b gene expression levels are upregulated in peripheral blood mononuclear cells from patients with acute myocarditis relative to healthy individuals. In addition, miR-208b levels have a prognostic value in the deterioration of left ventricular GLPS in those patients. Thus, miR-208b may represent a promising biomarkers in myocarditis or a potential therapeutic target in the future. Funding Acknowledgement Type of funding source: None


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Alexandra Muñoz ◽  
Max Costa

There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-αand is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs) of obese individuals. Specifically the upregulation ofCCL2/MCP-1,CCL3/MIP-1α,CCL4/MIP-1β,CXCL2/MIP-2α, andCXCL3/MIP-2βis noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs) both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.


Author(s):  
Marike M. Leijs ◽  
Lin Gan ◽  
Patrick De Boever ◽  
André Esser ◽  
Philipp M. Amann ◽  
...  

Polychlorinated biphenyls (PCBs) are well known carcinogenic persistent environmental pollutants and endocrine disruptors. Our aim was to identify the possible dysregulation of genes in PCB exposed peripheral blood mononuclear cells (PBMCs) in order to give more insight into the differential pathophysiological effects of PCB congeners and mixtures, with an emphasis on immunological effects and oxidative stress. The PBMCs of a healthy volunteer (male, 56 years old) were exposed to a mixture of dioxin-like (DL)-PCBs (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, 250 µg/L resp.) or non-dioxin-like (NDL)-PCBs (PCB 28, 52, 101, 138, 153, 180, 250 µg/L resp.) or single PCB congener (no.28, 138, 153, 180, 250 µg/L resp.). After an incubation period of 24 h, a microarray gene expression screening was performed, and the results were compared to gene expression in control samples (PBMCs treated with the vehicle iso-octane). Treatment of PBMCs with the DL-PCB mixture resulted in the largest number of differentially regulated genes (181 upregulated genes >2-fold, 173 downregulated >2-fold). Treatment with the NDL-PCB mix resulted in 32 upregulated genes >2-fold and 12 downregulated genes >2-fold. A gene set enrichment analysis (GSEA) on DL-PCB treated PBMCs resulted in an upregulation of 125 gene sets and a downregulation of 76 gene sets. Predominantly downregulated gene sets were involved in immunological pathways (such as response to virus, innate immune response, defense response). An upregulation of pathways related to oxidative stress could be observed for all PCB congeners except PCB-28; the latter congener dysregulated the least number of genes. Our experiment augments the information known about immunological and cellular stress responses following DL- as well as NDL-PCB exposure and provides new information on PCB 28. Further studies should be performed to evaluate how disruption of these pathways contributes to the development of autoimmune diseases and cancer.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Marketou ◽  
J Kontaraki ◽  
K Fragiadakis ◽  
J Konstantinou ◽  
S Maragkoudakis ◽  
...  

Abstract Purpose MicroRNAs (miRs) play a major role in protein regulation by post-transcriptional gene expression and cell to cell interaction. Recently, they have been emerged as important modulators in cardiovascular development and disease. Our aim was to determine whether cardiac related miRs such as miR-208b was differentially expressed in peripheral blood mononuclear cells from patients with acute myocarditis. We also evaluated their expression levels in peripheral blood mononuclear cells in relation with left ventricular global longitudinal peak strain (GLPS) in those patients. Methods We assessed the expression levels of miR-208b in 45 patients with acute myocarditis (38 men, mean age 31±10 years) and 22 healthy individuals (18 men, mean age 33±9 years). Blood samples were taken on admission and miR expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. All patients were also underwent an assessment with standard conventional transthoracic and a two-dimensional speckle tracking echocardiography. Results GLPS was significantly reduced in the group of myocarditis compared to healthy individuals (from −13.7 ± −7.9% versus −22.2±6.7%, p<0.05). Myocarditis patients showed significantly higher miR-208b (28.5±6.6 versus 6.40±1.1, p<0.001) expression levels compared to control group. miR-208b gene expression levels at baseline revealed a significant negative correlation with GLPS on admission (r=−0.51, p<0.05). This correlation was independent of the patients' clinical parameters. Conclusions Our data reveal that miR-208b gene expression levels are upregulated in peripheral blood mononuclear cells from patients with acute myocarditis relative to healthy individuals. In addition, miR-208b levels have a prognostic value in the deterioration of left ventricular GLPS in those patients. Thus, miR-208b may represent a promising biomarkers in myocarditis or a potential therapeutic target in the future.


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