scholarly journals MiRNA126 – RGS16 – CXCL12 Cascade as a Potential Mechanism of Acute Exercise-Induced Precursor Cell Mobilization

2021 ◽  
Vol 12 ◽  
Author(s):  
Michelle Schmid ◽  
Helena Caria Martins ◽  
Gerhard Schratt ◽  
Julia M. Kröpfl ◽  
Christina M. Spengler
Keyword(s):  
Peripheral Blood ◽  
Acute Exercise ◽  
Mononuclear Cells ◽  
Strongly Correlated ◽  
Potential Mechanism ◽  
Clinical Trial Registration ◽  
Peripheral Blood Mononuclear ◽  
Time Points ◽  
Cell Mobilization ◽  
Exercise Induced

Acute exercise enhances circulating stem and precursor cells (CPCs) in the peripheral blood. The responsible mechanisms and molecular pathways, however, have not been fully identified. The aim of the present study was to investigate a pathway related to elevated levels of apoptotic peripheral blood mononuclear cells (MNCs) and their secretome. An increased uptake of miRNA126 in MNCs was suggested to lead to reduced levels of RGS16 mRNA and, in turn, an enhanced translation and secretion of CXCL12. Eighteen healthy, young men underwent two identical incremental cycling exercises of which the first served as control while the second was preceded by a 7-day-long antioxidative supplementation. Blood samples were collected at baseline (−10min) and several time points after exercise (0, 30, 90, 180, and 270min). Relative concentrations of miRNA126 in MNCs and CXCL12 levels in plasma were determined at all time points while RGS16 mRNA was assessed in MNCs at baseline and 30min after exercise. CXCL12 increased after exercise and strongly correlated with CPC numbers. MiRNA126 increased 30min and, to a lesser extent, also 180 and 270min after exercise but only with supplementation. RGS16 mRNA decreased 30min after exercise independent of the intervention. The amount of RGS16 mRNA inversely correlated with levels of miRNA126, but not with plasma CXCL12. In conclusion, even though plasma CXCL12 correlated with CPC numbers, the increase in CXCL12 cannot be explained by the increased concentration of miRNA126 and lower RGS16 mRNA in MNCs that would have allowed for an enhanced translation of CXCL12.Clinical Trial Registration: ClinicalTrials.gov, NCT03747913. Registered 20 November 2018, https://clinicaltrials.gov/ct2/show/NCT03747913.

scholarly journals Integrated microRNA and mRNA Gene Expression in Peripheral Blood Mononuclear Cells in Response to Acute Psychosocial Stress: A Repeated-Measures Within-Subject Pilot Study

2021 ◽  
Author(s):  
Magdalena Maria Jurkiewicz ◽  
Anett Müller-Alcazar ◽  
Dirk Moser ◽  
Indralatha Jayatilaka ◽  
Anatoly Mikhailik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Psychosocial Stress ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Time Points ◽  
Blood Mononuclear Cells ◽  
The Impact ◽  
Acute Psychosocial Stress

Abstract Objective: The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points. Results: For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.

scholarly journals LncRNA and mRNA expression profile of peripheral blood mononuclear cells in primary Sjögren’s syndrome patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Peng ◽  
Xuan Luo ◽  
Yingying Chen ◽  
Linyi Peng ◽  
Chuiwen Deng ◽  
...  
Keyword(s):  
Immune Response ◽  
Expression Analysis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
Cell Metastasis ◽  
Blood Mononuclear Cells

AbstractThe aim of this study was to elucidate the expression profile and the potential role of long non-coding RNA (LncRNA) in the peripheral blood mononuclear cells of primary Sjögren’s syndrome (pSS) patients. RNA-seq technology was used to detect the differentially expressed LncRNAs and mRNAs between five age-and sex-matched paired pSS patients and healthy control PBMCs. The selected LncRNAs were detected in the validation study by RT-qPCR in 16 paired pSS patients and healthy controls. The GO, KEGG, co-localization, and co-expression analysis were performed to enrich the potential gene functions and pathways. In this study, 44 out of 1772 LncRNAs and 1034 out of 15,424 mRNAs were expressed differentially in the PBMCs of pSS patients. LINC00426, TPTEP1-202, CYTOR, NRIR, and BISPR were validated as aberrantly expressed, and these LncRNAs strongly correlated with disease activity of pSS. GO and KEGG pathway analysis revealed the significant enrichment of biological processes, cellular components, and molecular function of the up and down-regulated mRNAs, which were mainly concentrated in the immune response and immune system processes. Co-localization and co-expression analysis also revealed that differentially expressed LncRNAs in the PBMCs of pSS were strongly correlated to the mRNA functioning associated with immune response and cell metastasis. Numerous LncRNAs and mRNAs were found differentially expressed in the PBMCs of pSS patients, especially NRIR and BISPR; they interacted with the co-localized and co-expressed mRNAs, which might participate in the pathogenesis of pSS through the NF-κB, JAK-STAT, and other signaling pathways that regulate cell metastasis.

Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia

2015 ◽  
Vol 134 (4) ◽  
pp. 255-262 ◽  
Author(s):  
Maciej Grzywnowicz ◽  
Agnieszka Karczmarczyk ◽  
Katarzyna Skorka ◽  
Malgorzata Zajac ◽  
Joanna Zaleska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
Programmed Death ◽  
Distinct Disease ◽  
Programmed Death 1

Background: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. Methods: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. Results: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PD-L1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. Conclusion: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.

scholarly journals Integrated microRNA and mRNA gene expression in peripheral blood mononuclear cells in response to acute psychosocial stress: a repeated-measures within-subject pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Magdalena Maria Jurkiewicz ◽  
Anett Mueller-Alcazar ◽  
Dirk Alexander Moser ◽  
Indralatha Jayatilaka ◽  
Anatoly Mikhailik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Psychosocial Stress ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Time Points ◽  
Blood Mononuclear Cells ◽  
The Impact ◽  
Acute Psychosocial Stress

Abstract Objective The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points. Results For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.

scholarly journals Thawed and Washed Apheresis Products Keep an Excellent CD34+ Cells Viability for 24 Hours Using Either Voluven or Normal Saline Plus Albumin

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5738-5738
Author(s):  
Miguel Blanquer Blanquer ◽  
Carmen Alguero ◽  
Pilar Menchon ◽  
Assumpta Ferrer ◽  
Pilar Martínez Avilés ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Normal Saline ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Time Points ◽  
Cd34 Cells ◽  
Blood Mononuclear Cells ◽  
The Mean

Abstract Cryopreservation of products rich in progenitor cells is mandatory for the feasibility of autologous hematopietic progenitor cells transplants. The most used product nowadays is the apheresis of mobilized peripheral blood mononuclear cells. However, cryopreservation implies the use of cryoprotectant molecules, such as DMSO, that can be toxic for the patients. Moreover, the thawing of the product goes with some unavoidable cell death and liberation of cytoplasmic content such as cytokines to the medium. And so, adverse reactions during the product infusion are not infrequent. Our group has demonstrated that washing the thawed apheresis products both with Voluven or with normal saline plus 5% albumin (NSA) is able to almost completely avoid infusion reactions without losing CD34+ cells. Here we wanted to know whether it also had the benefit of extending CD34+ viability for 24 hours after washing. METHODS: We thawed 3 spare peripheral blood mononuclear cells apheresis products that had been cryopreserved with 9%DMSO. Ten mL of each product were separated and the remaining volume was splitted in 2 bags to be washed either with Voluven or NSA. Sepax 2 smartwash automatic program was used to wash the cells. The washed cells were stored at 4ºC and a sample was taken and immediately analyzed at 0h, 1h, 2h, 4h and 24h. At the same time points 10 mL of each bag were separated and kept 30 min. at room temperature (RT) before being analyzed. A blood count was performed on all the samples. Flow cytometry was used to measure CD45+ and CD34+ cells viability by 7AAD staining. RESULTS: The mean CD45+ cells viability was 69% after thawing the cells ,81% immediately after washing them with Voluven, and 81%, 80%, 79% and 73% 1h, 2h, 4h and 24h after the wash. When using NSA the mean CD45+ viability was 79%, 92%, 93%, 92%, 93% and 87% at the same time points. When the samples were kept for 30 additional minutes at RT, the mean CD45+ viability was 78%, 81%, 84%, 82%, 84% and 81% with Voluven, and 80%, 92%, 94%, 91%, 95% and 86% with NSA. Regarding CD34+ cells, when washed with Voluven the mean viability was 46%, 87%, 87%, 92%, 83% and 69%, while it was 61%, 91%, 91%, 92%, 89% and 84% when NSA was used. The mean CD34+ cells viability results after 30' at RT for each time point were 79%, 90%, 82%, 91%, 82% and 81% with Voluven and 85%, 90%, 90%, 94%, 93% and 86% with NSA. Moreover the mean viable CD34+ cells recovery at 24h was 90.94% for Voluven and 87,88% for NSA. CONCLUSIONS: We have obtained an excellent stability of the CD34+ cells viability for 24h after washing the mobilized mononuclear cells apheresis products both with Voluven and with NSA when the products are stored at 4ºC. Moreover, the viability is not affected when the cells are kept for an additional 30' at RT. The viable CD34+ cells loss at 24h was scarce. Disclosures Blanquer Blanquer: Pfizer: Research Funding.

Tissue factor-dependent pathway is not involved in exercise-induced formation of thrombin and fibrin

2002 ◽  
Vol 92 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Claus Weiss ◽  
Angelika Bierhaus ◽  
Ralf Kinscherf ◽  
Volker Hack ◽  
Thomas Luther ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Tissue Factor ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Exercise Induced ◽  
Dependent Pathway ◽  
Intensive Physical Exercise

In healthy individuals, prolonged intensive physical exercise leads to an activation of blood coagulation that results in the formation of thrombin and fibrin. This study investigated whether oxidative stress during intensive physical exercise induces tissue factor (TF) via activation of the redox-responsive transcription factor nuclear factor-κB (NF-κB). Twelve young men performed a standardized 1-h maximal run on a treadmill that gave rise to significant increases of markers of thrombin and fibrin formation. The ratio of intracellular reduced to oxidized glutathione as measured by HPLC decreased from 23.3 ± 10.7 to 14.2 ± 6.5 ( P < 0.05), indicating the generation of free radicals during exercise. Electrophoretic mobility shift assays from nuclear extracts of peripheral blood mononuclear cells revealed that exercise testing increased NF-κB (p50/p65) binding activity to a NF-κB consensus sequence by 105 ± 68% ( P < 0.01) but did not affect NF-κB (p65/c-Rel) binding to a nonconsensus-κB-like site present in the TF promoter. Consistently, there was no exercise-induced increase in TF expression as demonstrated by TF-specific immunofluorescence staining and ELISA. Thus selective activation of NF-κB (p50/p65) during intensive physical exercise does not result in the expression of TF, suggesting that the TF-dependent pathway in peripheral blood mononuclear cells does not account for exercise-induced formation of thrombin and fibrin.

Therapeutic and Immunoregulatory Effects of Tacrolimus in Patients with Refractory Generalized Myasthenia Gravis

2020 ◽  
Vol 83 (5) ◽  
pp. 500-507
Author(s):  
Hui Wu ◽  
Zhangyang Wang ◽  
Jianying Xi ◽  
Jue Liu ◽  
Chong Yan ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Peripheral Blood Lymphocytes ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Time Points ◽  
Quality Of Life Scale ◽  
Life Scale

<b><i>Objectives:</i></b> The aim of this study wasto investigate the efficacy of tacrolimus treatment in patients with refractory generalized myasthenia gravis (MG) and explore its impact on lymphocytic phenotypes and related cytokines mRNA expression. <b><i>Methods:</i></b> A total of 24 refractory generalized MG patients were enrolled. Before treatment and at 2, 6, and 12 months after tacrolimus treatment, the therapeutic effect was evaluated by the quantitative MG score of the Myasthenia Gravis Foundation of America (QMG), Manual Muscle Test (MMT), MG-specific Activities of Daily Living (MG-ADL), 15-item Myasthenia Gravis Quality-of-Life Scale (MG-QOL15), and changes of prednisone dosage. Also, we used the flow cytometer for the lymphocytic immunophenotyping and real-time PCR for the qualification of cytokine mRNA in peripheral blood mononuclear cells (PBMCs) at different time points during the treatment. <b><i>Results:</i></b> Significantly decreased QMG, MMT, MG-ADL, and MG-QOL15 were observed at all time points during the tacrolimus treatment. The dosage of prednisone also reduced at the end of the observation period with only 6 adverse events reported. The immunological impact of tacrolimus was revealed by reduced percentages of Tfh, Breg, CD19<sup>+</sup>BAFF-R<sup>+</sup> B cells, and increased percentages of Treg cells as well as down-regulated expression of IL-2, IL-4, IL-10, and IL-13 mRNA levels in PBMCs during the treatment. <b><i>Conclusion:</i></b> Our study indicated the clinical efficacy of tacrolimus in patients with refractory generalized MG. The underlying immunoregulatory mechanism of tacrolimus may involve alterations in the phenotypes of peripheral blood lymphocytes and Th1/Th2-related cytokine expression of PBMCs.

scholarly journals LncRNA and mRNA expression profile of peripheral blood mononuclear cells in primary Sjögren’s syndrome patients

2019 ◽  
Author(s):  
Yu Peng ◽  
Luo Xuan ◽  
Yingying Chen ◽  
Linyi Peng ◽  
Chuiwen Deng ◽  
...  
Keyword(s):  
Immune Response ◽  
Expression Analysis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
Cell Metastasis ◽  
Blood Mononuclear Cells

Abstract Background The aim of this study was to elucidate the expression profile and the potential role of long non-coding RNA (LncRNA) in the peripheral blood mononuclear cells of primary Sjögren’s syndrome (pSS) patients. Methods RNA-seq technology was used to detect the differentially expressed LncRNAs and mRNAs between five paired pSS patients and healthy control PBMCs. The selected LncRNAs were detected in the validation study by RT-qPCR in 16 paired pSS patients and healthy controls. The GO, KEGG, co-localization, and co-expression analysis were performed to enrich the potential gene functions and pathways.Results In this study, 44 out of 1772 LncRNAs and 1034 out of 15424 mRNAs were expressed differentially in the PBMCs of pSS patients. LINC00426, TPTEP1-202, CYTOR, NRIR, and BISPR were validated as aberrantly expressed, and these LncRNAs strongly correlated with disease activity of pSS. GO and KEGG pathway analysis revealed the significant enrichment of biological processes, cellular components, and molecular function of the up and down-regulated mRNAs, which were mainly concentrated in the immune response and immune system processes. Co-localization and co-expression analysis also revealed that differentially expressed LncRNAs in the PBMCs of pSS were strongly correlated to the mRNA functioning associated with immune response and cell metastasis. Conclusions Numerous LncRNAs and mRNAs were found differentially expressed in the PBMCs of pSS patients, especially NRIR and BISPR; they interacted with the co-localized and co-expressed mRNAs, which might participate in the pathogenesis of pSS through the NF-κB, JAK-STAT, and other signaling pathways that regulate cell metastasis.

Sign in / Sign up

Export Citation Format

Share Document