scholarly journals Gallop Racing Shifts Mature mRNA towards Introns: Does Exercise-Induced Stress Enhance Genome Plasticity?

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 410
Author(s):  
Katia Cappelli ◽  
Samanta Mecocci ◽  
Silvia Gioiosa ◽  
Andrea Giontella ◽  
Maurizio Silvestrelli ◽  
...  
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Coding Regions ◽  
Transcription Modulation ◽  
Response To Stress ◽  
Differential Gene ◽  
Exercise Induced ◽  
Regulatory Functions ◽  
Genomic Repeats

Physical exercise is universally recognized as stressful. Among the “sport species”, the horse is probably the most appropriate model for investigating the genomic response to stress due to the homogeneity of its genetic background. The aim of this work is to dissect the whole transcription modulation in Peripheral Blood Mononuclear Cells (PBMCs) after exercise with a time course framework focusing on unexplored regions related to introns and intergenic portions. PBMCs NGS from five 3 year old Sardinian Anglo-Arab racehorses collected at rest and after a 2000 m race was performed. Apart from differential gene expression ascertainment between the two time points the complexity of transcription for alternative transcripts was identified. Interestingly, we noted a transcription shift from the coding to the non-coding regions. We further investigated the possible causes of this phenomenon focusing on genomic repeats, using a differential expression approach and finding a strong general up-regulation of repetitive elements such as LINE. Since their modulation is also associated with the “exonization”, the recruitment of repeats that act with regulatory functions, suggesting that there might be an active regulation of this transcriptional shift. Thanks to an innovative bioinformatic approach, our study could represent a model for the transcriptomic investigation of stress.

Cardiac Sarcoidosis: Cytokine Patterns in the Course of the Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1207-1210 ◽  
Author(s):  
Michael Schoppet ◽  
Sabine Pankuweit ◽  
Bernhard Maisch
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Cardiac Sarcoidosis ◽  
Systemic Disease ◽  
Healing Process ◽  
Unknown Etiology ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rapid Decline ◽  
Peripheral Blood Mononuclear ◽  
Multiple Organs

Abstract Sarcoidosis is a chronic systemic disease of unknown etiology, which is characterized by noncaseating epitheloid granulomas usually in multiple organs. Here we describe changes in cytokine mRNA expression by peripheral blood mononuclear cells (PBMCs) and changes of cytokine protein levels in plasma over a time course of 12 months in a patient with sarcoidosis confined to the heart as diagnosed by endomyocardial biopsy. Mitogen-stimulated PBMCs exhibited a more TH1 cytokine profile at onset of symptoms before immunosuppressive therapy was initiated, with a change to a TH0 response in the course of the disease as evidenced by multiplex-polymerase chain reaction. In plasma, high levels of interleukin-6 could be detected by an enzyme-linked immunosorbent assay system, with rapid decline correlating with immunosuppression and improving clinical course. These changes may point to a role of TH1 and TH2 cytokines in the pathogenesis and the healing process of cardiac sarcoidosis.

scholarly journals Differential Gene Expression in Human Peripheral Blood Mononuclear Cells Induced by Cigarette Smoke and Its Constituents

2005 ◽  
Vol 86 (1) ◽  
pp. 200-210 ◽  
Author(s):  
Danitsja M. van Leeuwen ◽  
Ralph W. H. Gottschalk ◽  
Marcel H. van Herwijnen ◽  
Edwin J. Moonen ◽  
Jos C. S. Kleinjans ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Differential Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Differential Gene

scholarly journals E. coliEndotoxin Modulates the Expression of Sirtuin Proteins in PBMC in Humans

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Angela Storka ◽  
Gerhard Führlinger ◽  
Martin Seper ◽  
Lisa Wang ◽  
Michael Jew ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Peripheral Blood Mononuclear ◽  
Human Endotoxemia ◽  
Lps Challenge ◽  
Endotoxemia Model ◽  
Regulatory Functions

Background. Sirtuin (SIRT) proteins are class I histone deacetylases displaying gene regulatory functions in inflammatory, cancer, and metabolic diseases. These SIRT actions involve the nuclear factorκB and its inhibitor IκB pathway. However, the regulation of SIRTin vivois still unclear.Material and Methods. In a human endotoxemia model, 20 healthy male subjects received an intravenous bolus of 2 ng/kg body weightEscherichia coliendotoxin (LPS). SIRT expression was investigated in peripheral blood mononuclear cells (PBMC) with qPCR and Western blot before and 3 hours, 6 hours, and 24 hours after LPS challenge. Additionally, SIRT regulation was studiedin vitroin cultivated PBMC after incubation with 20 ng/mL LPS.Results. A downregulation by >40% of SIRT1 mRNA was detectable 3 hours after LPS and of SIRT3 mRNA 6 hours after LPS. SIRT3, IκBα, and IκB-βprotein expressions were decreased 3 and 6 hours after LPS. SIRT2 mRNA or protein expression did not change following LPS. These findings were consistentin vitroand associated with augmented phosphorylation of IκB-β.Discussion. In thisE. coliendotoxemia model, SIRT1 and SIRT3 mRNA expressions in PBMC in humans were reduced after LPS challenge. This suggests that SIRT may represent an inflammatory target proteinin vivo.

scholarly journals Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation

2015 ◽  
Vol 59 (10) ◽  
pp. 6080-6086 ◽  
Author(s):  
Laura Dickinson ◽  
H. Manisha Yapa ◽  
Akil Jackson ◽  
Graeme Moyle ◽  
Laura Else ◽  
...  
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Geometric Mean ◽  
Treatment Interruption ◽  
Drug Intake ◽  
Peripheral Blood Mononuclear ◽  
Preexposure Prophylaxis ◽  
Tenofovir Df ◽  
H 41 ◽  
Tenofovir Diphosphate

ABSTRACTPharmacokinetic (PK) data describing a prolonged time course of antiretrovirals in plasma and peripheral blood mononuclear cells (PBMCs) are important for understanding and managing late or missed doses and to assess the appropriateness of compounds for preexposure prophylaxis (PrEP). This study aimed to evaluate the PK of coformulated tenofovir disoproxil fumarate (DF), emtricitabine, and rilpivirine in plasma and of the intracellular (IC) anabolites tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in healthy volunteers up to 9 days after drug cessation. Individuals received daily tenofovir DF-emtricitabine-rilpivirine (245/200/25 mg) for 14 days. Drug intake was stopped, and serial sampling occurred prior to the final dose and up to 216 h (9 days) after stopping drug intake. Concentrations were quantified and PK parameters calculated. Eighteen volunteers completed the study. The terminal elimination plasma half-lives for tenofovir and emtricitabine over 216 h (geometric mean [90% confidence interval]) were higher than those seen over 0 to 24 h (for tenofovir, 31 h [27 to 40 h] versus 13.3 h [12.5 to 15.1 h]; for emtricitabine, 41 h [36 to 54 h] versus 6.4 h (5.9 to 7.6 h]). Model-predicted IC half-lives (0 to 168 h) were 116 h (TFV-DP) and 37 h (FTC-TP). The plasma rilpivirine concentration at 216 h was 4.5 ng/ml (4.2 to 6.2 ng/ml), and half-lives over 0 to 216 h and 0 to 24 h were 47 h (41 to 59 h) and 35 h (28 to 46 h), respectively. These data contribute to our understanding of drug behavior following treatment interruption; however, adherence to therapy should be promoted. Validated plasma and IC target concentrations are necessary to allow interpretation with respect to sustained virus suppression or HIV prevention. (The trial was conducted in accordance with the Declaration of Helsinki [EudraCT 2012-002781-13].)

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.

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