scholarly journals Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage

2020 ◽  
Vol 21 (18) ◽  
pp. 6870 ◽  
Author(s):  
Zsolt Fejes ◽  
Judit Erdei ◽  
Marianna Pócsi ◽  
Jun Takai ◽  
Viktória Jeney ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Preterm Infants ◽  
Intraventricular Hemorrhage ◽  
Inflammatory Cell ◽  
Cell Culture Supernatant ◽  
Protein Biomarkers ◽  
Choroid Plexus Epithelial Cell ◽  
Soluble Adhesion Molecules ◽  
Inflammatory Conditions

Intraventricular hemorrhage (IVH) represents a high risk of neonatal mortality and later neurodevelopmental impairment in prematurity. IVH is accompanied with inflammation, hemolysis, and extracellular hemoglobin (Hb) oxidation. However, microRNA (miRNA) expression in cerebrospinal fluid (CSF) of preterm infants with IVH has been unknown. Therefore, in the present study, candidate pro-inflammatory cell-free miRNAs were analyzed in CSF samples from 47 preterm infants with grade III or IV IVH vs. clinical controls (n = 14). miRNAs were quantified by RT-qPCR, normalized to “spike-in” cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry as well as IL-8, VCAM-1, ICAM-1, and E-selectin concentrations by ELISA. To reveal the origin of the investigated miRNAs, controlled hemolysis experiments were performed in vitro; in addition, human choroid plexus epithelial cell (HCPEpiC) cultures were treated with metHb, ferrylHb, heme, or TNF-α to replicate IVH-triggered cellular conditions. Levels of miR-223, miR-155, miR-181b, and miR-126 as well as Hb metabolites along with IL-8 were elevated in CSF after the onset of IVH vs. controls. Significant correlations were observed among the miRNAs, oxidized Hb forms, and the soluble adhesion molecules. During the post-IVH follow-up, attenuated expression of miRNAs and protein biomarkers in CSF was observed upon elimination of Hb metabolites. These miRNAs remained unaffected by a series of artificially induced hemolysis, which excluded red blood cells as their origin, while stimulation of HCPEpiCs with oxidized Hb fractions and heme resulted in increased extracellular miRNA levels in the cell culture supernatant. Overall, the hemorrhage-induced CSF miRNAs reflected inflammatory conditions as potential biomarkers in preterm IVH.

scholarly journals CYCLIC AMP IN CEREBROSPINAL FLUID (CSF) OF PRETERM INFANTS WITH INTRAVENTRICULAR HEMORRHAGE / POST-HEMORRHAGIC HYDROCEPHALUS (IVH/PHH).† 2259

1996 ◽  
Vol 39 ◽  
pp. 379-379
Author(s):  
Massroor Pourcyrous ◽  
Helena Parfenova ◽  
Momoh Yakubu ◽  
Henrietta S Bada ◽  
Sheldon B Korones ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclic Amp ◽  
Preterm Infants ◽  
Intraventricular Hemorrhage

scholarly journals Long Noncoding RNAs in Urine Are Detectable and May Enable Early Detection of Acute T Cell–Mediated Rejection of Renal Allografts

2015 ◽  
Vol 61 (12) ◽  
pp. 1505-1514 ◽  
Author(s):  
Johan M Lorenzen ◽  
Celina Schauerte ◽  
Malte Kölling ◽  
Anika Hübner ◽  
Monika Knapp ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Noncoding Rnas ◽  
Kidney Injury ◽  
Long Noncoding Rnas ◽  
Cell Culture Supernatant ◽  
Transplant Patients ◽  
Inflammatory Conditions ◽  
And Control

AbstractBACKGROUNDLong noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. They are detectable in the blood of patients with acute kidney injury. We tested whether lncRNAs are present in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection.METHODSA global lncRNA expression analysis was performed with RNA from urine of patients with acute T cell–mediated renal allograft rejection and control transplant patients. Deregulated lncRNAs were confirmed in kidney biopsies and urine in a validation cohort of 62 patients with acute rejection, 10 of them after successful antirejection therapy, and 31 control transplant patients.RESULTSA global screen revealed several lncRNAs to be deregulated in urine of patients with acute rejection. Three intergenic lncRNAs, LNC-MYH13-3:1, RP11-395P13.3-001, and RP11-354P17.15-001, were most strongly altered. These were validated in the whole cohort of patients. RP11-395P13.3-001 and RP11-354P17.15-001 were upregulated in patients with acute rejection compared with controls. Only levels of RP11-354P17.15-001 normalized in patients with acute rejection after successful antirejection therapy. RP11-354P17.15-001 was associated with higher decline in glomerular filtration rate 1 year after transplantation. In vitro, in tubular epithelial cells, all lncRNAs were enriched by interleukin-6 treatment, but only RP11-395P13.3-001 and RP11-354P17.15-001 increased in cell culture supernatant, indicating that these lncRNAs might be secreted under inflammatory conditions.CONCLUSIONSlncRNAs are strongly altered in urine of patients with acute rejection. Urinary RP11-354P17.15-001 may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

scholarly journals Design, Synthesis and Biological Evaluation of Arylpyridin-2-yl Guanidine Derivatives and Cyclic Mimetics as Novel MSK1 Inhibitors. An Application in an Asthma Model

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 391
Author(s):  
Maud Bollenbach ◽  
Simona Nemska ◽  
Patrick Wagner ◽  
Guillaume Camelin ◽  
François Daubeuf ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Inflammatory Diseases ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Cell Recruitment ◽  
Inflammatory Conditions ◽  
Asthma Model ◽  
Inflammatory Cell Recruitment ◽  
Synthesis And Biological Evaluation

Mitogen- and Stress-Activated Kinase 1 (MSK1) is a nuclear kinase, taking part in the activation pathway of the pro-inflammatory transcription factor NF-kB and is demonstrating a therapeutic target potential in inflammatory diseases such as asthma, psoriasis and atherosclerosis. To date, few MSK1 inhibitors were reported. In order to identify new MSK1 inhibitors, a screening of a library of low molecular weight compounds was performed, and the results highlighted the 6-phenylpyridin-2-yl guanidine (compound 1a, IC50~18 µM) as a starting hit for structure-activity relationship study. Derivatives, homologues and rigid mimetics of 1a were designed, and all synthesized compounds were evaluated for their inhibitory activity towards MSK1. Among them, the non-cytotoxic 2-aminobenzimidazole 49d was the most potent at inhibiting significantly: (i) MSK1 activity, (ii) the release of IL-6 in inflammatory conditions in vitro (IC50~2 µM) and (iii) the inflammatory cell recruitment to the airways in a mouse model of asthma.

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

Osteopathic status of preterm infants with intraventricular hemorrhage

2020 ◽  
pp. 64-73
Author(s):  
L. K. Karimova ◽  
J. O. Kuzmina ◽  
Z. N. Zinnurova ◽  
E. M. Vasilevskaja
Keyword(s):  
Preterm Infants ◽  
Intraventricular Hemorrhage

Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Alzheimer’s Disease

2018 ◽  
Vol 15 (13) ◽  
pp. 1244-1260 ◽  
Author(s):  
Mirjana Babić Leko ◽  
Magdalena Krbot Skorić ◽  
Nataša Klepac ◽  
Fran Borovečki ◽  
Lea Langer Horvat ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Tau Protein ◽  
Strong Correlation ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Protein Biomarkers ◽  
Related Potentials ◽  
T Tau

Introduction: The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD. Aims: The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid β peptide (β1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients. Subjects: The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia. Results: ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aβ1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients. Conclusion: Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.

scholarly journals Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions

2021 ◽  
pp. 1-17
Author(s):  
Stefan Bernhard ◽  
Stefan Hug ◽  
Alexander Elias Paul Stratmann ◽  
Maike Erber ◽  
Laura Vidoni ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Severe Trauma ◽  
Induced Response ◽  
Neutrophil Granulocytes ◽  
Inflammatory Conditions ◽  
Flow Cytometric ◽  
Time Flow ◽  
Flow Cytometric Measurement ◽  
Detailed Kinetics

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pH<sub>i</sub>) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pH<sub>i</sub>, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.

scholarly journals Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1123
Author(s):  
Wendy C. Ziai ◽  
Adrian R. Parry-Jones ◽  
Carol B. Thompson ◽  
Lauren H. Sansing ◽  
Michael T. Mullen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intraventricular Hemorrhage ◽  
Inflammatory Responses ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drainage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Injury Reduction ◽  
Positive Correlations ◽  
Factor Α ◽  
Perihematomal Edema

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.

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