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MicroRNA AND sepsis

Jingjing Wu, Yini Wang, Lanjuan Li
The nanoparticles referred as exosomes play an active role in intercellular communication. Their potential positive therapeutic effect in bacterial inflammation and sepsis has been the subject of several studies that have examined the feasibility of exosomes as drug-delivery vehicles. The underlying mechanism of interest involves the selective transport of cellular cargo. Most attention has been focused on the exosome-mediated transport of microRNA and protein. Thus, exosomes are expected to be an important tool in the treatment of inflammatory disease...
October 27, 2016: Biochimica et Biophysica Acta
Jeffery Ho, Hung Chan, Sunny H Wong, Maggie H T Wang, Jun Yu, Zhangang Xiao, Xiaodong Liu, Gordon Choi, Czarina C H Leung, Wai T Wong, Zheng Li, Tony Gin, Matthew T V Chan, William K K Wu
BACKGROUND: Sepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis. METHODS: We searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words ("microRNA", "long non-coding RNA", "circular RNA", "sepsis" and/or "septic shock") from inception to Sep 2016...
November 28, 2016: Critical Care: the Official Journal of the Critical Care Forum
Mihnea Dragomir, Dragoş George Emil Petrescu, Graţiela Elena Manga, George A Călin, Cătălin Vasilescu
The risks that arise after splenectomy can be divided in infectious and non-infectious. The link between splenectomy and these hazards remains partially unknown. Host defense against infection is altered after splenectomy and such individuals develop sepsis more easily and the infection has a fulminant course. Splenectomy is also a potential risk factor for several vascular complications that result from partial or total obstruction of an arterial or venous blood vessel. Furthermore, pulmonary hypertensioncan be a severe and sometimes fatal complication following splenectomy...
2016: Chirurgia
Dana Elena Giza, Enrique Fuentes-Mattei, Marc David Bullock, Stefan Tudor, Matthew Joseph Goblirsch, Muller Fabbri, Florea Lupu, Sai-Ching Jim Yeung, Catalin Vasilescu, George Adrian Calin
Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities. Biomarkers are potentially valuable clinical tools in this context, but to date, no single biomarker has been shown to perform adequately. Hence, in an effort to discover novel diagnostic and prognostic markers in sepsis, new genomic approaches have been employed...
December 2016: Cell Death and Differentiation
Hui Wang, Yihua Bei, Peipei Huang, Qiulian Zhou, Jing Shi, Qi Sun, Jiuchang Zhong, Xinli Li, Xiangqing Kong, Junjie Xiao
Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects...
October 11, 2016: Molecular Therapy. Nucleic Acids
He Ma, Xiaohui Wang, Tuanzhu Ha, Ming Gao, Li Liu, Ruitao Wang, Kaijiang Yu, John H Kalbfleisch, Race L Kao, David L Williams, Chuanfu Li
BACKGROUND:  This study examined the effect of microRNA-125b (miR-125b) on sepsis-induced cardiac dysfunction. METHODS:  Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 days before cecal ligation and puncture (CLP)-induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group). Survival was monitored following CLP-induced sepsis (n = 12/group). RESULTS:  LmiR-125b transfection significantly attenuated cardiac dysfunction due to CLP-induced sepsis...
December 1, 2016: Journal of Infectious Diseases
Geoffrey N Hendy, Lucie Canaff
The human calcium-sensing receptor gene (CASR) has 8 exons, and localizes to chromosome 3q. Exons 1A and 1B encode alternative 5'-untranslated regions (UTRs) that splice to exon 2 encoding the AUG initiation codon. Exons 2-7 encode the CaSR protein of 1078 amino acids. Promoter P1 has TATA and CCAAT boxes upstream of exon 1A, and promoter P2 has Sp1/3 motifs at the start site of exon 1B. Exon 1A transcripts from the P1 promoter are reduced in parathyroid tumors and colon carcinomas. Studies of colon carcinomas and neuroblastomas have emphasized the importance of epigenetic changes-promoter methylation of the GC-rich P2 promoter, histone acetylation-as well as involvement of microRNAs in bringing about CASR gene silencing and reduced CaSR expression...
2016: Frontiers in Physiology
Michael A Makara, Ky V Hoang, Latha P Ganesan, Elliot D Crouser, John S Gunn, Joanne Turner, Larry S Schlesinger, Peter J Mohler, Murugesan V S Rajaram
BACKGROUND: Sepsis patients with cardiac dysfunction have significantly higher mortality. Although several pathways are associated with myocardial damage in sepsis, the precise cause(s) remains unclear and treatment options are limited. This study was designed to develop a new model to investigate the early events of cardiac damage during sepsis progression. METHODS AND RESULTS: Francisella tularensis subspecies novicida (Ft.n) is a Gram-negative intracellular pathogen causing severe sepsis syndrome in mice...
September 2016: Journal of the American Heart Association
Xiao Wang, Liangliang Hao, Heng-Fu Bu, Alexander W Scott, Ke Tian, Fangyi Liu, Isabelle G De Plaen, Yulan Liu, Chad A Mirkin, Xiao-Di Tan
Milk fat globule-EGF factor 8 (MFG-E8) maintains the intestinal homeostasis by enhancing enterocyte migration and attenuating inflammation. We previously reported that sepsis is associated with down-regulation of intestinal MFG-E8 and impairment of enterocyte migration. Here, we showed that impairment of intestinal epithelial cell migration occurred in lipopolysaccharide (LPS)-induced septic mice. Treatment of RAW264.7 cells (a murine macrophage-like cell line) with LPS increased expression of miR-99b, a microRNA that is predicted to target mouse MFG-E8 3'UTR...
2016: Scientific Reports
Marius Papurica, Alexandru F Rogobete, Dorel Sandesc, Raluca Dumache, Carmen A Cradigati, Mirela Sarandan, Radu Nartita, Sonia E Popovici, Ovidiu H Bedreag
BACKGROUND: The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient...
2016: Clinical Laboratory
David H Jang, John C Greenwood, Meghan B Spyres, David M Eckmann
Metabolic biomarkers have potentially wider use in disease diagnosis and prognosis as well as in monitoring disease response to treatment. While biomarkers such as interleukins, microRNA, and lactate have been proposed for disease surveillance, there are still conflicting results regarding their clinical utility. Treatment of commonly encountered disease of acute care such as sepsis, trauma, and poisoning often relies on clinical diagnosis and therapy guided by use of surrogate markers of illness severity. The measurement of mitochondrial function, including respiration and motility, may offer superior alternatives to such markers...
January 2017: Journal of Intensive Care Medicine
Haihuan Lin, Zexun Mo, Heyi Su, Zhenhui Guo
Sepsis is as life-threatening organ failure caused by a dysregulated host response to infection, with urgent onset, complex mechanism and high mortality. Its early diagnosis and treatment is particularly important. However, the sensitivity and specificity of current laboratory markers for the diagnosis of sepsis is not ideal. MicroRNAs represent a novel group of small RNA molecules that do not encode for proteins. MicroRNAs are synthesized in the cytoplasm and transferred to circulation primarily by micro-vesicles, and they are stable in circulation and can be rapidly detected...
August 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Chao Lan, Xiaopeng Shi, Nannan Guo, Hui Pei, Huali Zhang
OBJECTIVE: To explore the value of serum microRNA-155-5p and -133a-3p (miR-155-5p and miR-133a-3p) expression for the diagnosis and prognosis evaluation of sepsis. METHODS: A prospective observational study was conducted. 105 sepsis patients admitted to emergency intensive care unit (EICU) of the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2016 were enrolled. They were divided into three groups according to the severity: 35 patients with sepsis, 35 with severe sepsis, and 35 with septic shock...
August 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Clara McClure, Melissa B McPeak, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Myeloid-derived suppressor cells (MDSCs) increase late sepsis immunosuppression and mortality in mice. We reported that microRNA (miR) 21 and miR-181b expression in Gr1(+)CD11b(+) myeloid progenitors increase septic MDSCs in mice by arresting macrophage and dendritic cell differentiation. Here, we report how sepsis regulates miR-21 and miR-181b transcription. In vivo and in vitro binding studies have shown that C/EBPα transcription factor, which promotes normal myeloid cell differentiation, binds both miRNA promoters in Gr1(+)CD11b(+) cells from sham mice...
January 2017: Immunology and Cell Biology
Yangzhou Liu, Ning Han, Qinchuan Li, Zengchun Li
The present study aimed to investigate the regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor (TNF)-α genetic variations. The GSE5760 expression profile data, which was downloaded from the Gene Expression Omnibus database, contained 30 wild-type (WT) and 28 mutation (MUT) samples. Differentially expressed genes (DEGs) between the two types of samples were identified using the Student's t-test, and the corresponding microRNAs (miRNAs) were screened using WebGestalt software...
July 2016: Experimental and Therapeutic Medicine
Stefano Caserta, Florian Kern, Jonathan Cohen, Stephen Drage, Sarah F Newbury, Martin J Llewelyn
Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied...
2016: Scientific Reports
Jörn-Hendrik Weitkamp, Scott O Guthrie, Hector R Wong, Lyle L Moldawer, Henry V Baker, James L Wynn
BACKGROUND: Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis. AIMS: To define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis...
July 2016: Early Human Development
Wenhai Zhou, Jing Wang, Zhifeng Li, Jianguo Li, Ming Sang
Inflammatory cytokines belonging to high mobility group box (HMGB)1 play a key role in sepsis through yet unknown mechanisms. The inflammatory response is modulated by microRNAs (miRNAs or miRs) at multiple levels and is poorly understood. In this study, the regulation of HMGB1 by miRNAs was evaluated using 3-(2,4-dimethoxybenzylidene)anabaseine (GTS-21) to activate the cholinergic anti-inflammatory pathway (CAP) and decrease HMGB1 expression in RAW264.7 cells. Microarray-based miRNA expression profiling of RAW264...
July 2016: International Journal of Molecular Medicine
Faisal Aziz
Since their discovery of more than a decade ago, microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Specific microRNAs have emerged as key players in disease biology by playing crucial role in disease development and progression. This review draws attention to miR-223 that has been reported to be abnormally expressed in several diseases like diabetes-type2, sepsis, rheumatoid arthritis, viral infections likes' human immunodeficiency virus-1 (HIV-1) and inflammatory disorders...
May 2016: Cellular Immunology
Yao-Li Cui, Bing Wang, Hong-Mei Gao, Ying-Hong Xing, Jian Li, Hong-Jie Li, Zhu Lin, Yong-Qiang Wang
BACKGROUND: Thrombocytopenia is one of the most common laboratory abnormalities encountered in patients with severe sepsis. It has been reported that thrombocytopenia is linked to mortality in patients with severe sepsis. However, the mechanism of thrombocytopenia in sepsis is unknown. We hypothesized that inflammatory cytokines and microRNAs (miRNAs) are not only involved in the pathogenesis of sepsis, but also are correlated with thrombocytopenia. PATIENTS AND METHODS: Eligible patients with severe sepsis were prospectively recruited and treated at our hospital between June 2012 and May 2014...
2016: Patient Preference and Adherence
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