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MicroRNA AND sepsis

Juliana Monte Real, Ludmila Rodrigues Pinto Ferreira, Gustavo Henrique Esteves, Fernanda Christtanini Koyama, Marcos Vinícius Salles Dias, João Evangelista Bezerra-Neto, Edécio Cunha-Neto, Flavia Ribeiro Machado, Reinaldo Salomão, Luciano Cesar Pontes Azevedo
BACKGROUND: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock...
March 15, 2018: Critical Care: the Official Journal of the Critical Care Forum
Yin Li, Fengxia Zhang, Yan Cong, Yun Zhao
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...
March 1, 2018: Molecular Medicine Reports
Haiju Zhang, Hui Li, Aamir Shaikh, Yi Caudle, Baozhen Yao, Deling Yin
Background: microRNA-23b (miR-23b) is a multiple functional miRNA. We hypothesize that miR-23b plays a role in the pathogenesis of sepsis. Our study investigated the effect of miR-23b on sepsis induced immunosuppression. Methods: Mice were treated with miR-23b inhibitors by tail vein injection 2 days after cecal ligation puncture (CLP)-induced sepsis. Apoptosis in spleens and apoptotic signals were detected, meanwhile survival was monitored. T cell immunoreactivities were examined in late sepsis...
March 1, 2018: Journal of Infectious Diseases
Ning Gao, Lei Dong
AIMS: The purpose of this study was to investigate the functional role of microRNA (miR)-146 in sepsis, as well as the underlying mechanism. METHODS: Human vascular endothelial cell line EA. hy926 cells were treated with lipopolysaccharide (LPS) and/or transfected with miR-146 mimics, inhibitor, and their corresponding controls. Expression of miR-146 was then analyzed after treatment and/or transfection, as well as the expression of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and E-selectin, and nuclear factor kappa B (NF-κB) binding activity...
November 1, 2017: Die Pharmazie
Shuying Yang, Yongqiang Wang, Hongmei Gao, Bing Wang
The aim of the present study was to explain the mechanism of miR-30a-3p overexpression in sepsis-induced cell apoptosis in vitro and in vivo. For the in vitro cell experiments, H9c2 cells were divided into three groups, including the untreated normal control (NC), lipopolysaccharide (LPS)-treated and miRNA (treated with LPS and transfection with miRNA-30a-3p) groups. The cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The relative protein expression levels were measured by western blot assay...
February 2018: Experimental and Therapeutic Medicine
Jun Zhou, Hongtao Chen, Youling Fan
Acute kidney injury (AKI) is a common and serious disease characterized by a rapid decline in renal function and has an unacceptably high mortality rate with no effective treatment beyond supportive care. AKI can be induced by many factors such as ischemia/reperfusion (IR), sepsis, and drug-induced nephrotoxicity. However, the molecular mechanisms of AKI are poorly understood. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein. NcRNAs play multiple roles in cellular processes, and mutations or imbalances of these molecules within the body can cause a variety of diseases...
November 21, 2017: Oncotarget
Yiping Li, Yanhong Li, Zhenjiang Bai, Jian Pan, Jian Wang, Fang Fang
BACKGROUND: Sepsis represents a complex disease with the dysregulated inflammatory response and high mortality rate. The goal of this study was to identify potential transcriptomic markers in developing pediatric sepsis by a co-expression module analysis of the transcriptomic dataset. METHODS: Using the R software and Bioconductor packages, we performed a weighted gene co-expression network analysis to identify co-expression modules significantly associated with pediatric sepsis...
December 13, 2017: Journal of Translational Medicine
Tie-Ning Zhang, Da Li, Jing Xia, Qi-Jun Wu, Ri Wen, Ni Yang, Chun-Feng Liu
Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities caused by an altered systemic host response to infection, has become the main cause of death among patients admitted to the intensive care units. Recently, genome-wide expression analysis revealed that over 80% of the essential genetic elements were altered in critically ill patients. Notably, non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, have been proven to play essential roles in innate immunity, mitochondrial dysfunction and organ dysfunction...
October 31, 2017: Oncotarget
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Claudio Ronco
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells...
November 22, 2017: Blood Purification
Qiu Yang, Dongshan Zhang, Ya Li, Yongquan Li, Yinpeng Li
Excessive inflammatory response and apoptosis play an important role in the sepsis-induced liver injury. Paclitaxel, a diterpene alkaloid of Taxus brevifolia, is widely used as an anti-tumor drug and shows protective effects on acute lung and kidney injury. However, whether it has a protective effect against sepsis-induced liver injury has not been reported. The objective of this study was to investigate the protective effects of paclitaxel in septic liver injury in mice and associated molecular mechanisms...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yun Ge, Man Huang, Yue-Feng Ma
BACKGROUND: Notch-1/NF-κB signaling plays a key role in the cecal ligation and puncture (CLP)-induced sepsis. This study aims to investigate the intervention effects of microRNA-34a (miR-34a) lentivirus regulating Notch-1/NF-κB signaling pathway on lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were divided into four groups as the following: they were infected with negative control lentivirus (NC group) or miR-34a lentivirus (OE group); LPS (1 μg/mL) was added on the third day on the basis of NC group and OE group for 24 hours (NC+LPS group or OE+LPS group)...
2017: World Journal of Emergency Medicine
Jing Zhu, Fu-Li Wang, Hai-Bin Wang, Ning Dong, Xiao-Mei Zhu, Yao Wu, Yong-Tao Wang, Yong-Ming Yao
Dendritic cell (DC) can be stimulated by both exogenous pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) and endogenous damage-associated molecular patterns (DAMPs) such as high mobility group box-1 protein (HMGB1). MicroRNAs (miRNAs) act as post-transcriptional fine tuners of mRNA. Studies have focused mostly on the potential role of miRNAs in DCs maturation triggered by PAMPs, especially LPS, however, little is known about the regulatory mechanism underlying the effects of miRNAs in DC maturation mediated by DAMPs, including HMGB1...
September 25, 2017: Scientific Reports
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs...
November 2017: Molecular Immunology
Yijun Zhang, Caixia Gan, Jiangbo Zhang, Dong Chen
Angiopoietin‑1 (ANG‑1), a ligand of the endothelial cell‑specific TIE2 surface receptor, acts in a complementary and coordinated manner with vascular endothelial growth factor during the process of angiogenesis. ANG‑1 can be used as a clinically informative biomarker of disease severity and outcome in severe sepsis. The epithelium‑specific Ets transcription factor 1 can activate ANG‑1 transcription in the setting of inflammation; however, relatively little is known about the regulation of ANG‑1 by microRNAs (miRs)...
November 2017: Molecular Medicine Reports
Zhaozhong Zhu, Liming Liang, Ruyang Zhang, Yongyue Wei, Li Su, Paula Tejera, Yichen Guo, Zhaoxi Wang, Quan Lu, Andrea A Baccarelli, Xi Zhu, Ednan K Bajwa, B Taylor Thompson, Guo-Ping Shi, David C Christiani
BACKGROUND: MicroRNAs (miRNAs) can play important roles in inflammation and infection, which are common manifestations of acute respiratory distress syndrome (ARDS). We assessed if whole blood miRNAs were potential diagnostic biomarkers for human ARDS. METHODS: This nested case-control study (N = 530) examined a cohort of ARDS patients and critically ill at-risk controls. Whole blood miRNA profiles and logistic regression analyses identified miRNAs correlated with ARDS...
August 30, 2017: Intensive Care Medicine Experimental
Consolato Sergi, Fan Shen, David W Lim, Weiyong Liu, Mingyong Zhang, Brian Chiu, Vijay Anand, Ziyong Sun
Subcellular dysfunction and impaired metabolism derived from the complex interaction of cytokines and mediators with cellular involvement are on the basis of the cardiovascular response to sepsis. The lethal consequences of an infection are intimately related to its ability to spread to other organ sites and the immune system of the host. About one century ago, William Osler (1849-1919), a Canadian physician, remarkably defined the sequelae of the host response in sepsis: "except on few occasions, the patient appears to die from the body's response to infection rather than from it...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Catalin Vasilescu, Mihnea Dragomir, Mihai Tanase, Dana Giza, Raluca Purnichescu-Purtan, Meng Chen, Sai-Ching Jim Yeung, George A Calin
Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and treatment. A large panel of small non-coding microRNAs was reported to modulate the immune response in sepsis but have not been tested in clinical practice. Large-scale identification of microRNA networks in sepsis might reveal a new biological mechanism that can be also targeted by gene therapy. Therefore, the main objective of this study is to perform a comparison of the miRNA network between septic patients and healthy controls...
2017: PloS One
Peng Wang, Xue Zhang, Fulun Li, Kai Yuan, Maoran Li, Jiwei Zhang, Bin Li, Wei Liang
Endothelial cell (EC) activation and dysfunction have been linked to a wide variety of vascular inflammatory diseases. However, the role of microRNAs in EC activation and inflammation remains largely unknown. In this study, we found that miR-130b was significantly decreased in human umbilical vein endothelial cells (HUVECs) after lipopolysaccharides (LPS) treatment. Forced expression of miR-130b inhibited the LPS-induced activation of extracellular signal-regulated kinase (ERK) and the inflammatory genes expression, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α)...
July 28, 2017: International Immunopharmacology
Liang Xu, Weijun Zhang, Renhua Sun, Jingquan Liu, Jun Hong, Qian Li, Bangchuan Hu, Fangxiao Gong
IGF-1 functions as an anti-oxidative stress molecule and some critical patients with sepsis have a lower level of serum IGF-1. However, the association between IGF-1 and the severity or prognosis of sepsis remains unclear. This study aimed to elucidate the relationship between serum IGF-1 levels and the severity and prognosis of sepsis, and the possible mechanism was analyzed. Clinical characteristics of patients with sepsis were recorded and analyzed. Serum IGF-1 levels and micro (mi)RNA-1 levels were tested using radioimmunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively...
July 2017: Experimental and Therapeutic Medicine
Dagmar Pfeiffer, Eva Roßmanith, Ingrid Lang, Dieter Falkenhagen
microRNAs (miRNAs) play an essential role in inflammation processes including sepsis. This study aimed to identify miRNAs as candidates for therapies that are involved in the innate immune response and to assess their potential functions in the activation of the endothelium. We stimulated THP-1 monocytes with 10 ng/ml LPS for 4 h and used the supernatant for the stimulation of human umbilical vein endothelial cells (HUVEC) or human pulmonary microvascular endothelial cells (HPMEC) for 16 h. miRNA array analysis (of 1,891 miRNAs) identified a 1...
2017: PloS One
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