The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Ho, Jeffery; Chan, Hung; Wong, Sunny H.; Wang, Maggie Haitian; Yu, Jun; Xiao, Zhangang; Liu, Xiao Dong; Choi, Gordon; Leung, C.C.H.; Wong, Wai Tat; Zheng, Lirong; Gin, Tony; Chan, Matthew T.V.; Wu, William Ka Kei

doi:10.1186/s13054-016-1555-3

Cited by 82 publications

(86 citation statements)

References 154 publications

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“…While highly accurate, the time to analysis can take days to weeks, whole genome sequencing is costly, and it can also identify commensals that may not be related to the disease. Deep sequencing technologies have also been used to determine epigenetic changes due to sepsis such as DNA methylation [58], histone modification [59], oxidative base damage [60] and mirRNA, ncRNA and mitochondrial RNA expression [61]. These emerging studies could provide unique insight in the disease process.…”

Section: System Biology Analysis Of Clinical Samples Provides Uniquementioning

confidence: 99%

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Wong

2017

Mol Diagn Ther

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Sepsis remains one of the leading causes of death in the United States and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug resistant organisms (MDROs). There is a dire need for the development of new antibiotics, improved antibiotic stewardship and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic and proteomic platforms have allowed for a broad spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic data sets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we will highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis.

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Section: System Biology Analysis Of Clinical Samples Provides Uniquementioning

confidence: 99%

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Wong

2017

Mol Diagn Ther

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“…MicroRNA is known to be one kind of noncoding RNAs that can regulate specific genes expression posttranscriptionally by targeting their mRNAs. Recent studies have revealed that numerous microRNAs involved in the process of sepsis and associated immune suppression, organ malfunction, and metabolism dysregulation [18][19][20][21][22]. These microRNAs serve as either extracellular or intracellular effector molecules targeting special mRNAs to manipulate metabolism and function of cells.…”

Section: Introductionmentioning

confidence: 99%

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

Lin

Liu

Wang

et al. 2019

BioMed Research International

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Objective. Sepsis and associated acute kidney injury (SAKI) are determined to be closely related to poor prognosis. Because the metabolic alterations of tubular epithelial cells (TECs) are crucial for the occurrence and development of SAKI, we carried out this present study to identify the metabolism changes of TECs during SAKI and relevant mechanisms. Methods. Rat SAKI model and rat tubular epithelial cell line were used in our study. ELISA was used to determine the serum cytokines levels. Protein expressions were examined with Western-Blotting and the transcriptions of RNAs were determined with qRT-PCR. ADP/ATP assay and Oil Red O staining were used to examine the energy and lipid metabolism, respectively. Dual-luciferase reporter assay was carried out to determine the interactions between miRNA and specific proteins. Cell cycle arrest and apoptosis were determined with flow cytometry. Results. Sepsis and AKI were induced 12 h after CLP. Energy and lipid metabolism reduced significantly while FOXO1 levels increased remarkably in TECs during SAKI. The expressions of both AKT and CDK2 and the transcriptions of relevant mRNAs reduced significantly in TECs during SAKI while miR-21-3p expression increased remarkably. Both AKT and CDK2 were determined as the direct targets of miR-21-3p. Furthermore, by in vitro experiments, it was demonstrated that FOXO1 levels were regulated by miR-21-3p in TECs via AKT/CDK2 and AKT/CDK2-FOXO1 pathway was crucial in the regulations of miR-21-3p on lipid metabolism, cell cycle arrest, and apoptosis of TECs. Conclusions. MiR-21-3p mediates metabolism and cell fate alterations of TECs via manipulating AKT/CDK2-FOXO1 pathway, and that is crucial in the regulation of energy metabolism of TECs during SAKI.

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“…Biochemical processes for the biosynthesis of microRNAs. microRNA-124 interactions [130][131][132], microRNA-181 interactions [133][134], microRNA-10a interactions [135][136][137], microRNA-21 interactions [138][139][140][141][142], microRNA-92a interactions [142][143], microRNA-125b, microRNA-130a, microRNA-210 [144][145][146][147][148].…”

Section: Micrornas Expression In Sepsis-induced By Cannabinoid Signalmentioning

confidence: 99%

Cannabis Sativa Revisited - Crosstalk between microRNAs Expression, Inflammation, Oxidative Stress and Endocannabinoid Response System in Critically Ill Patients with Sepsis

Rogobete¹,

Bratu²,

Bedreag³

et al. 2019

Preprint

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Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levelsThe aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression. cascade and in the evolution of sepsis are represented by the inflammatory response, immune response, and redox activity, followed by the involvement of cellular defects, which all lead to severe organ dysfunction. Adding to this phenomenon are severe respiratory infections; tissue hypoxia; acute kidney injury (AKI); metabolic imbalances; and, last but not least, derangements of the biological system as a whole. Through the augmentation of the inflammatory status and through the concomitant derangement of several organ functions, a high percentage of critical patients with sepsis develop multiple organ dysfunction syndrome (MODS), and finally death [8,[10][11][12].Numerous biochemical and cellular systems involved in sepsis pathogenesis have been studied, both in order to better understand these complex mechanisms, and in the hope of finding new therapeutic targets. The endocannabinoid response system is one of them. Recent studies have shown the involvement of specific endocannabinoid receptors, such as endocannabinoid CB1 receptor and CB2 receptor, as well as their link with important processes in sepsis, such as the immune response, inflammatory response, and redox activity [13]. Furthermore, a series of implications on the epigenetic processes have also been proven, through the change in the microRNAs expression, the microRNAs responsible for the modulation of the immune, and inflammatory systems [14]. It was also shown that by stimulatin...

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The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Cited by 82 publications

References 154 publications

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

Cannabis Sativa Revisited - Crosstalk between microRNAs Expression, Inflammation, Oxidative Stress and Endocannabinoid Response System in Critically Ill Patients with Sepsis

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