scholarly journals Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

2014 ◽  
Vol 126 (12) ◽  
pp. 857-867 ◽  
Author(s):  
Hui-juan Wang ◽  
Bao-zeng Wang ◽  
Peng-jun Zhang ◽  
Jie Deng ◽  
Zhi-rui Zhao ◽  
...  

Four novel protein biomarkers encoded by the miRNA target genes were identified for patients with sepsis. The combined analysis of the four proteins indicated that their predictive value for sepsis prognosis was better than the values for the SOFA score and APACHE II score.

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Walid H Nofal ◽  
Sahar K Abo Alela ◽  
Moustafa M Aldeeb ◽  
Gamal M Elewa

Abstract Background Despite all worldwide efforts towards sepsis, more than 5.3 million patients die annually. Till now, there is no parameter or score to detect mortality in septic patients precisely. Objectives The aim of this study was to evaluate the prognostic performance of the lactate/albumin (L/A) ratio when combined with APACHE II score, SOFA score and SAPS II for predicting 28-day mortality in critically ill patients with septic shock. Patients and Methods After approval of the Medical Ethics Committee of Ain Shams Faculty of Medicine, an informed consent was taken from the patient or next of kin to include his/her data in this study. All patients who were admitted to the intensive care units (ICUs) with septic shock from 1st of September, 2019 to 30th of March, 2020 were assessed for enrollment in this study. Results In this prospective observational study, 100 adult patients of both sexes with septic shock were enrolled. They were categorized into two groups according to the primary endpoint (outcome) “28-days mortality”. Sixty-one patients (61%) died (non-survivors’ group) and thirtynine patients (39%) survived (survivors group). The most significant factors which affecting the mortality were LAR, SOFA score on admission, APACHE II, and SAPS II score. Prediction performance of the four variables for estimating 28 days mortality. When combined LAR + SOFA, LAR + APACHE, LAR + SAPS II, Overall score the ROC (AUROC, 0.867,0.847,0.849,,0.899 respectively) was the highest, compared to the other single models and lower cutoff (>0.48, >0.53, >0.42, >0.47 respectively)in comparison to single scores. Moreover, the overall score (including the 4 parameters together) gave the best predictive value for 28 day mortality Conclusion Lactate/Albumin ratio combined with APACHI II, SOFA and SAPS scores gave the best predictive value for 28 day mortality in septic shock patients, when compared with each separate score Recommendations combined LAR + SOFA, LAR + APACHE, LAR + SAPS II, Overall score recommended to use to predictho spital mortality, Further research on large sample sizeto study the risk stratification and implementing new scores using the lactate/albumin ratio (LAR) is needed. Simple, available and cheap markers should be used in developing new prediction scores.


2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.


2021 ◽  
Vol 160 (6) ◽  
pp. S-312-S-313
Author(s):  
Sandra R. Gomez ◽  
Eric Lam ◽  
Luis Gonzalez Mosquera ◽  
Joshua Fogel ◽  
Paul Mustacchia

2010 ◽  
Vol 136 (8) ◽  
pp. 1151-1159 ◽  
Author(s):  
Xiaonan Kang ◽  
Lu Sun ◽  
Kun Guo ◽  
Hong Shu ◽  
Jun Yao ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenyu Li ◽  
Hongxia Wang ◽  
Jian Liu ◽  
Bing Chen ◽  
Guangping Li

Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.Methods. A total of 102 patients with sepsis were divided into survival group (n=60) and nonsurvival group (n=42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05).Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.


Author(s):  
J T Whicher ◽  
C E Spence

The predictive value of plasma protein changes in disease is very largely unknown, as relevant clinical and laboratory studies are lacking. The usefulness of zone electrophoresis as a method of detecting a constellation of plasma protein changes is even less clear. With the advent of precise automated techniques for specific plasma protein measurement, zone electrophoresis has little to offer except in the identification and quantitation of paraproteins, where it is essential.


2021 ◽  
Vol 10 (3) ◽  
pp. 495
Author(s):  
Juhyun Song ◽  
Hanjin Cho ◽  
Dae Won Park ◽  
Sungwoo Moon ◽  
Joo Yeong Kim ◽  
...  

Vasoactive and inotropic medications are essential for sepsis management; however, the association between the maximum Vasoactive-Inotropic score (VISmax) and clinical outcomes is unknown in adult patients with sepsis. We investigated the VISmax as a predictor for mortality among such patients in the emergency department (ED) and compared its prognostic value with that of the sequential organ failure assessment (SOFA) score. This single-center retrospective study included 910 patients diagnosed with sepsis between January 2016 and March 2020. We calculated the VISmax using the highest doses of vasopressors and inotropes administered during the first 6 h on ED admission and categorized it as 0–5, 6–15, 16–30, 31–45, and >45 points. The primary outcome was 30-day mortality. VISmax for 30-day mortality was significantly higher in non-survivors than in survivors. The mortality rates in the five VISmax groups were 17.2%, 20.8%, 33.3%, 54.6%, and 70.0%, respectively. The optimal cut-off value of VISmax to predict 30-day mortality was 31. VISmax had better prognostic value than the cardiovascular component of the SOFA score and initial lactate levels. VISmax was comparable to the APACHE II score in predicting 30-day mortality. Multivariable analysis showed that VISmax 16–30, 31–45, and >45 were independent risk factors for 30-day mortality. VISmax in ED could help clinicians to identify sepsis patients with poor prognosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinghua Gao ◽  
Li Zhong ◽  
Ming Wu ◽  
Jingjing Ji ◽  
Zheying Liu ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) has spread around the world, until now, the number of positive and death cases is still increasing. Therefore, it remains important to identify risk factors for death in critically patients. Methods We collected demographic and clinical data on all severe inpatients with COVID-19. We used univariable and multivariable Cox regression methods to determine the independent risk factors related to likelihood of 28-day and 60-day survival, performing survival curve analysis. Results Of 325 patients enrolled in the study, Multi-factor Cox analysis showed increasing odds of in-hospital death associated with basic illness (hazard ratio [HR] 6.455, 95% Confidence Interval [CI] 1.658–25.139, P = 0.007), lymphopenia (HR 0.373, 95% CI 0.148–0.944, P = 0.037), higher Sequential Organ Failure Assessment (SOFA) score on admission (HR 1.171, 95% CI 1.013–1.354, P = 0.033) and being critically ill (HR 0.191, 95% CI 0.053–0.687, P = 0.011). Increasing 28-day and 60-day mortality, declining survival time and more serious inflammation and organ failure were associated with lymphocyte count < 0.8 × 109/L, SOFA score > 3, Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 7, PaO2/FiO2 < 200 mmHg, IL-6 > 120 pg/ml, and CRP > 52 mg/L. Conclusions Being critically ill and lymphocyte count, SOFA score, APACHE II score, PaO2/FiO2, IL-6, and CRP on admission were associated with poor prognosis in COVID-19 patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lauren K Truby ◽  
Jessica A Regan ◽  
Maggie Nguyen ◽  
Stephani Giamberardino ◽  
Robert J Mentz ◽  
...  

Introduction: To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM). Hypothesis: Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with DM. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling (>700 proteins) on 440 paired cases and matched controls from placebo-assigned participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Cases were defined as having met the primary composite outcome of MACE or incident HFH and matched to controls on baseline prevalent heart failure, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Conditional logistic regression was used to determine the association between log-transformed relative protein expression and incident MACE or HFH. False-discovery-rate (FDR) was used to adjust for multiple comparisons. Results: We identified three specific proteins that were significantly associated with prevalent MACE or HFH: METRNL, Notch 3, and ROR1 (OR 2.1, 1.6, 1.7 and q-value 0.01, 0.02, and 0.05 respectively) (Figure 1). METRNL, in particular, performed similarly to the established biomarker NT-proBNP (Figure 1). When MACE and HFH were analyzed separately, METRNL, in particular, remained strongly associated with both outcomes (OR 2.0, p<0.001 and OR 2.7, p=0.05). Conclusions: Three novel protein biomarkers, in particular METRNL (a circulating adipokine that regulates insulin-sensitivity), may identify diabetic patients at high risk for subsequent HF and MACE. Additional studies are needed to replicate these findings and uncover the biologic mechanism linking adipokine signaling and heart failure.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Sriparna Mukherjee ◽  
Irshad Akbar ◽  
Reshma Bhagat ◽  
Bibhabasu Hazra ◽  
Arindam Bhattacharyya ◽  
...  

ABSTRACT RNA viruses are known to modulate host microRNA (miRNA) machinery for their own benefit. Japanese encephalitis virus (JEV), a neurotropic RNA virus, has been reported to manipulate several miRNAs in neurons or microglia. However, no report indicates a complete sketch of the miRNA profile of neural stem/progenitor cells (NSPCs), hence the focus of our current study. We used an miRNA array of 84 miRNAs in uninfected and JEV-infected human neuronal progenitor cells and primary neural precursor cells isolated from aborted fetuses. Severalfold downregulation of hsa-miR-9-5p, hsa-miR-22-3p, hsa-miR-124-3p, and hsa-miR-132-3p was found postinfection in both of the cell types compared to the uninfected cells. Subsequently, we screened for the target genes of these miRNAs and looked for the biological pathways that were significantly regulated by the genes. The target genes involved in two or more pathways were sorted out. Protein-protein interaction (PPI) networks of the miRNA target genes were formed based on their interaction patterns. A binary adjacency matrix for each gene network was prepared. Different modules or communities were identified in those networks by community detection algorithms. Mathematically, we identified the hub genes by analyzing their degree centrality and participation coefficient in the network. The hub genes were classified as either provincial (P < 0.4) or connector (P > 0.4) hubs. We validated the expression of hub genes in both cell line and primary cells through qRT-PCR after JEV infection and respective miR mimic transfection. Taken together, our findings highlight the importance of specific target gene networks of miRNAs affected by JEV infection in NSPCs. IMPORTANCE JEV damages the neural stem/progenitor cell population of the mammalian brain. However, JEV-induced alteration in the miRNA expression pattern of the cell population remains an open question, hence warranting our present study. In this study, we specifically address the downregulation of four miRNAs, and we prepared a protein-protein interaction network of miRNA target genes. We identified two types of hub genes in the PPI network, namely, connector hubs and provincial hubs. These two types of miRNA target hub genes critically influence the participation strength in the networks and thereby significantly impact up- and downregulation in several key biological pathways. Computational analysis of the PPI networks identifies key protein interactions and hubs in those modules, which opens up the possibility of precise identification and classification of host factors for viral infection in NSPCs.


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