The Use of Exosomes as Biomarkers for Evaluating and Monitoring Critically Ill Polytrauma Patients with Sepsis

Ticlea, Marian; Bratu, Lavinia Melania; Bodog, Florian Dorel; Bedreag, Ovidiu Horea; Rogobete, Alexandru Florin; Crăiniceanu, Zorin

doi:10.1007/s10528-016-9773-6

Cited by 8 publications

(10 citation statements)

References 44 publications

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“…Zhao et al also found that the serum levels of miR-150 decreased in a rat sepsis model, providing a valuable tool in evaluating the prognosis of sepsis ( 11 ). Similarly, the expression of miR-150 was reported to be decreased in a patient with sepsis ( 46 ). A previous study found that MLCK , including MYLK1, MYLK2 and MYLK3 , may not upregulate endothelial permeability induced by LPS exposure, whereas hyper-permeability was observed in sepsis and other inflammatory situations ( 47 ).…”

Section: Discussionmentioning

confidence: 95%

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

et al. 2018

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Sepsis is a type of systemic inflammatory response syndrome caused by infection. The present study aimed to examine key genes and microRNAs (miRNAs) involved in the pathogenesis of sepsis. The GSE13205 microarray dataset, downloaded from the Gene Expression Omnibus was analyzed using bioinformatics tools, and included muscle biopsy specimens of 13 patients with sepsis and eight healthy controls. The differentially expressed genes (DEGs) in samples from patients with sepsis were identified using the Linear Models for Microarray package in R language. Using the Database for Annotation, Visualization and Integration Discovery tool, functional and pathway enrichment analyses were performed to examine the potential functions of the DEGs. The protein-protein interaction (PPI) network was constructed with the DEGs using the Search Tool for the Retrieval of Interacting Genes, and the network topology was analyzed using CytoNCA. Subsequently, MCODE in Cytoscape was used to identify modules in the PPI network. Finally, the integrated regulatory network was constructed based on the DEGs, miRNAs and transcription factors (TFs). A total of 259 upregulated DEGs (MYC and BYSL) and 204 downregulated DEGs were identified in the patients with sepsis. NOP14, NOP2, AATF, GTPBP4, BYSL and TRMT6 were key genes in the MCODE module. In the integrated DEG-miRNA-TF regulatory network, hsa-miR-150 (target gene MYLK3) and 21 TFs, comprising 14 upregulated DEGs (including MYC) and seven downregulated DEGs, were identified. The results suggested that NOP14, NOP2, AATF, GTPBP4, BYSL, MYC, MYLK3 and miR-150 may be involved in the pathogenesis of sepsis.

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Section: Discussionmentioning

confidence: 95%

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

et al. 2018

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“…This reaction takes place only if it is catalyzed by the DiGeorge Syndrome Critical Region 8 (DGCR8). [43][44][45][46] The transporting protein, Exportin 5, will then act on the pre-miRNAs, which will transfer the epigenetic complex from the nucleus to the cell cytoplasm. [47][48][49] Once the signal that the complex has reached the cytoplasm is received, RNA polymerase III (Dicer) and trans-activator RNA binding protein (TRBP) attack it and lead to the formation of mature miRNAs.…”

Section: The Most Common Molecular Mechanisms Involved In Cvdsmentioning

confidence: 99%

Nuclear Transcription Factor Kappa B (NF-кB) and Molecular Damage Mechanisms in Acute Cardiovascular Diseases. A Review

Buzaș

Rogobete

Popovici

et al. 2018

Journal of Cardiovascular Emergencies

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Worldwide, cardiovascular diseases (CVDs) represent one of the main causes of morbidity and mortality, and acute coronary syndromes are responsible for a large number of sudden cardiac deaths. One of the main challenges that still exist in this area is represented by the early detection and targeted monitoring of the pathophysiology involved in CVDs. During the last couple of years, researchers have highlighted the importance of molecular and epigenetic mechanisms involved in the initiation and augmentation of CVDs, culminating in their most severe form represented by acute myocardial infarction. One of the most studied molecular factors involved in this type of pathology is represented by nuclear transcription factor kappa B (NF-κB), as well as the involvement of microRNAs (miRNAs). It has been suggested that miRNAs can also be involved in the complex process of atheromatous plaque vulnerabilization that leads to an acute cardiac event. In this review paper, we describe the most important molecular mechanisms involved in the pathogenesis of CVDs and atheromatous plaque progression and vulnerabilization, which include molecular mechanisms dependent on NF-κB. For this paper, we used international databases (PubMed and Scopus). The keywords used for the search were “miRNAs biomarkers”, “miRNAs in cardiovascular disease”, “NF-κB in cardiovascular disease”, “molecular mechanism in cardiovascular disease”, and “myocardial NF-κB mechanisms”. Numerous molecular reactions that have NF-κB as a trigger are involved in the pathogenesis of CVDs. Moreover, miRNAs play an important role in initiating and aggravating certain segments of CVDs. Therefore, miRNAs can be used as biomarkers for early evaluation of CVDs. Furthermore, in the future, miRNAs could be used as a targeted molecular therapy in order to block certain mechanisms responsible for inducing CVDs and leading to acute cardiovascular events.

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“…From a molecular point of view, microRNAs are synthesized in the cell nucleus through the action of RNA polymerase II on certain specific genes. Hence, the initial species, the pri-microRNAs, are formed following complex reactions [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35]. In the next step, RNAse III endonuclease, also called Drosha, activates the pri-microRNAs.…”

Section: Biochemical and Biosynthesis Aspects Of Micrornasmentioning

confidence: 99%

“…A series of complex mechanisms involved in the pathophysiology and biochemistry of sepsis have been studied for the past several years. However, the critically ill polytrauma patient is so complex biochemically and molecularly that no specific biochemical pathways have been found in which intervention could increase survival rates, or decrease the incidence of sepsis and multiple organ dysfunction syndrome (MODS) [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25]. However, in the last few years, a series of microRNA epigenetic species have been identified.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, numerous studies have shown the importance of microRNAs in early diagnosis and possible future epigenetic therapies [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33]. By examining microRNAs with respect to critically ill polytrauma patients, we can see important links between the development and modulation of the systemic inflammatory response, the immune system, coagulation status, and response to infections [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. The paper aims to systematize the microRNA expressions that are closely related to the pathophysiological events involved in a critically ill polytrauma patient with sepsis.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients

Rogobete

Săndesc

Bedreag

et al. 2018

Cells

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A critically ill polytrauma patient is one of the most complex cases to be admitted to the intensive care unit, due to both the primary traumatic complications and the secondary post-traumatic interactions. From a molecular, genetic, and epigenetic point of view, numerous biochemical interactions are responsible for the deterioration of the clinical status of a patient, and increased mortality rates. From a molecular viewpoint, microRNAs are one of the most complex macromolecular systems due to the numerous modular reactions and interactions that they are involved in. Regarding the expression and activity of microRNAs in sepsis, their usefulness has reached new levels of significance. MicroRNAs can be used both as an early biomarker for sepsis, and as a therapeutic target because of their ability to block the complex reactions involved in the initiation, maintenance, and augmentation of the clinical status.

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The Use of Exosomes as Biomarkers for Evaluating and Monitoring Critically Ill Polytrauma Patients with Sepsis

Cited by 8 publications

References 44 publications

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

Nuclear Transcription Factor Kappa B (NF-кB) and Molecular Damage Mechanisms in Acute Cardiovascular Diseases. A Review

MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients

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