scholarly journals Reduced Maternal Circulating Cell‐Free Mitochondrial DNA Is Associated With the Development of Preeclampsia

2022 ◽  
Author(s):  
Spencer C. Cushen ◽  
Contessa A. Ricci ◽  
Jessica L. Bradshaw ◽  
Talisa Silzer ◽  
Alexandra Blessing ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Penalized Regression ◽  
Circulating Dna ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Absolute Concentrations

Background Circulating cell‐free mitochondrial DNA (ccf‐mtDNA) is a damage‐associated molecular pattern that reflects cell stress responses and tissue damage, but little is known about ccf‐mtDNA in preeclampsia. The main objectives of this study were to determine (1) absolute concentrations of ccf‐mtDNA in plasma and mitochondrial DNA content in peripheral blood mononuclear cells and (2) forms of ccf‐mtDNA transport in blood from women with preeclampsia and healthy controls. In addition, we sought to establish the association between aberrance in circulating DNA‐related metrics, including ccf‐mtDNA and DNA clearance mechanisms, and the clinical diagnosis of preeclampsia using bootstrapped penalized logistic regression. Methods and Results Absolute concentrations of ccf‐mtDNA were reduced in plasma from women with preeclampsia compared with healthy controls ( P ≤0.02), while mtDNA copy number in peripheral blood mononuclear cells did not differ between groups ( P >0.05). While the pattern of reduced ccf‐mtDNA in patients with preeclampsia remained, DNA isolation from plasma using membrane lysis buffer resulted in 1000‐fold higher ccf‐mtDNA concentrations in the preeclampsia group ( P =0.0014) and 430‐fold higher ccf‐mtDNA concentrations in the control group ( P <0.0001). Plasma from women with preeclampsia did not induce greater Toll‐like receptor‐9–induced nuclear factor kappa‐light‐chain enhancer of activated B cells‐dependent responses in human embryonic kidney 293 cells overexpressing the human TLR‐9 gene ( P >0.05). Penalized regression analysis showed that women with preeclampsia were more likely to have lower concentrations of ccf‐mtDNA as well as higher concentrations of nuclear DNA and DNase I compared with their matched controls. Conclusions Women with preeclampsia have aberrant circulating DNA dynamics, including reduced ccf‐mtDNA concentrations and DNA clearance mechanisms, compared with gestational age–matched healthy pregnant women.

scholarly journals Altered expression of the DISC1 gene in peripheral blood of patients with schizophrenia

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoqian Fu ◽  
Guofu Zhang ◽  
Yansong Liu ◽  
Ling Zhang ◽  
Fuquan Zhang ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Neuronal Morphology ◽  
Antipsychotic Treatment ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Blood Mononuclear Cells ◽  
Before And After

Abstract Background Schizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients. Methods In this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis. Results The expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01). Conclusions Our study provided further support for the involvement of DISC1 in the development of schizophrenia.

scholarly journals The Expression and Pathophysiological Role of Osteopontin in Graves' Disease

2011 ◽  
Vol 96 (11) ◽  
pp. E1866-E1870 ◽  
Author(s):  
Lingyan Xu ◽  
Xinran Ma ◽  
Yanyan Wang ◽  
Xiaoli Li ◽  
Yicheng Qi ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Graves Disease ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Pathophysiological Role ◽  
Blood Mononuclear Cells

Abstract Context: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory cytokine production. Osteopontin (OPN), an extracellular matrix protein of pleiotropic properties, has recently been recognized as a potent inflammatory cytokine in several autoimmune diseases. Objective: This study sought to explore the pathophysiological role of OPN in GD by comparing OPN levels in initial GD patients and healthy controls. Methods: Seventy-six patients who met criteria for initial GD and sixty-five healthy controls were recruited. OPN and other clinical GD diagnosis parameters were measured. In addition, the coexpression of several OPN receptors as well as various nuclear factor-κB (NF-κB) downstream target genes were examined in peripheral blood mononuclear cells from human subjects. The effect of OPN on NF-κB activation was determined by in vitro assays. Results: We demonstrated for the first time that the OPN levels are enhanced in serum from GD patients. OPN levels are strongly associated with clinical serum parameters for GD diagnosis. The coexpression of selective OPN receptors and inflammatory response genes was enhanced in peripheral blood mononuclear cells from GD patients. Furthermore, serum from GD patients activated NF-κB activity in vitro, which was significantly suppressed by OPN monoclonal antibody abrogation. Conclusion: These data indicated a clinical correlation between serum OPN levels and GD. OPN could affect GD development through NF-κB activation and the subsequent changes in inflammatory milieu. OPN could serve as a novel biomarker for GD as well as a potential target for GD treatment.

GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells

2014 ◽  
Vol 10 (9) ◽  
pp. 2398-2406 ◽  
Author(s):  
Mei-Ling Liu ◽  
Peng Zheng ◽  
Zhao Liu ◽  
Yi Xu ◽  
Jun Mu ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Metabolic Profiling ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Novel Biomarkers ◽  
Metabolomic Approach

A GC-MS based metabolomic approach was applied to characterize the metabolic profiling of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia.

Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Hiroshi Otsu ◽  
Mikio Watanabe ◽  
Naoya Inoue ◽  
Ryota Masutani ◽  
Yoshinori Iwatani
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Intraindividual Variation ◽  
Autoimmune Thyroid Diseases ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Autoimmune Thyroid ◽  
Blood Mononuclear Cells

AbstractBackground:microRNAs (miRNAs) circulate in the blood and negatively regulate the expression of mRNAs. Some miRNAs are associated with the development of autoimmune thyroid diseases (AITD); however, there are few reports on the association between miRNA expression and the pathogenesis of AITD or the physiological variations of circulating miRNAs, which are important to examine as biomarkers.Methods:We examined the circadian and day-to-day variations in the expression levels of 5 miRNAs (miR-125a, miR-146a, miR-155, let-7e and miR-106a) in plasma and peripheral blood mononuclear cells (PBMC). We also analysed the expression levels of two of these miRNAs (miR-146a and miR-155) in 20 healthy controls, 60 Graves’ disease (GD) patients and 50 Hashimoto’s disease (HD) patients.Results:For each miRNA, we observed wide intraindividual variation [coefficient of variation value (CV): 70%–100%] compared to measurement error (CV: 20%–40%). In patients with AITD, HD, GD in remission and mild HD, the expression levels of miR-146a in PBMC were increased 296%, 328%, 348% and 464% above the levels in healthy controls, respectively (p=0.0443 and p=0.0273, p=0.0267 and p=0.0052, respectively). In severe HD, the expression level of miR-155 in plasma was increased to 347% of that in healthy controls (p=0.0256).Conclusions:The expression levels of miRNAs in plasma and PBMC showed wide intraindividual variation. In addition, miR-146a may be associated with the development of AITD.

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