Stroke is a devastating cerebrovascular pathology with high morbidity and mortality. Inflammation plays a central role in the pathophysiology of stroke. Vagus nerve stimulation (VNS) is a promising immunomodulatory method that has shown positive effects in stroke treatment, including neuroprotection, anti-apoptosis, anti-inflammation, antioxidation, reduced infarct volume, improved neurological scores, and promotion of M2 microglial polarization. In this review, we summarize the current knowledge about the vagus nerve's immunomodulatory effects through the cholinergic anti-inflammatory pathway (CAP) and provide a comprehensive assessment of the available experimental literature focusing on the use of VNS in stroke treatment.
Cíl: Cílem studie bylo prozkoumat změny v expresi pro-zánětlivého a pro-apoptotického cytokinu tumor nekrotizující faktor alfa (TNFα) a mikroRNA (miRNA), které se podílejí na jeho regulaci v časném období po subarachnoidálním krvácení (SAK). Soubor a metodika: Exprese miRNA (miR-125b, miR-146a, miR-346, miR-155, miR-15b) a mRNA (TNFα) byly stanoveny pomocí kvantitativní polymerázové řetězové reakce v reálném čase z mozkové tkáně experimentálních zvířat. Celkem 88 zvířat bylo rozděleno do skupin Sham (kontrolní operace bez indukce SAK), Lehké SAK, Těžké SAK, do časových intervalů 2, 4, 6 a 8 h (n = 7 ve skupině); 4 zvířata byla použita jako absolutní kontrola. Výsledky: Byly nalezeny statisticky významné rozdíly v expresi TNFα mezi skupinami Sham a Těžké SAK ve všech zkoumaných časových intervalech (p < 0,05), dále mezi skupinami Sham a Lehké SAK 4 h po indukci SAK (p < 0,05) a mezi skupinami Lehké SAK a Těžké SAK ve 2 a 6h časovém intervalu (p < 0,05). Dále byl pozorován významný rozdíl v expresi miRNA-15b mezi skupinami Sham a Těžké SAK 8 h po začátku SAK (p < 0,05). U dalších analyzovaných miRNA jsme v expresi nepozorovali žádné statisticky významné změny. Závěr: SAK bylo asociováno s časným nárůstem exprese TNFα a miR-15b, zejména u skupiny Těžké SAK. Navzdory komplexitě vzájemné regulace mezi cytokiny a mikroRNA, může informace o časné aktivaci zánětlivých/apoptotických mechanismů několik hodin po SAK přispět k lepšímu poznání patofyziologie SAK. Pochopení mechanismů vzájemné regulace proapoptotických markerů TNFα a miR-15b může přispět ke zlepšení terapie této závažné patologie.
Aim: The aim of the study was to investigate expression changes of pro-inflammatory and pro-apoptotic cytokine tumor necrosis factor alpha (TNFα) and microRNAs (miRNAs) involved in its regulation in early pathophysiological changes after subarachnoid haemorrhage (SAH). Materials and methods: MiRNAs (miR-125b, miR-146a, miR-346, miR-155, miR-15b) and mRNA (TNFα) expression were determined by quantitative real-time polymerase chain reaction in brain tissue samples. A total of 88 animals were divided to Sham (control surgery without induction of SAH), Mild SAH, Severe SAH groups in following time-points: 2, 4, 6 and 8 h (n = 7 per group); including 4 animals used as an absolute control. Results: We have found a statistically significant difference in TNFα expression between Sham and Severe SAH groups at all the time-points (p < 0.05), between Sham and Mild SAH groups 4 h after induction of SAH (p < 0.05) and between Mild and Severe SAH groups at 2 and 6 h time-points (p < 0.05). Furthermore, a significant difference in miR-15b expression between Sham and Severe SAH groups was observed 8 h after SAH (p < 0.05). All the other microRNAs have not been significantly changed. Conclusions: SAH was associated with an early increase in TNFα and miR-15b expression especially in Severe SAH group. Despite complex cross-regulation between cytokines and miRNA, any information about the activation of inflammation/apoptotic mechanisms within a few hours after SAH may improve our knowledge of SAH pathophysiology. Furthermore, it can lead to therapeutic improvement using a combination of both pro-apoptotic markers TNFα and miR-15b.
- Klíčová slova
- časné poškození mozku, perforační model,
- MeSH
- apoptóza MeSH
- mikro RNA MeSH
- modely nemocí na zvířatech MeSH
- mozek patologie MeSH
- potkani Sprague-Dawley MeSH
- subarachnoidální krvácení * patologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.
OBJECTIVE: To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs). MATERIALS AND METHODS: Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n = 16) and without (n = 14) preterm premature rupture of membranes (PPROM). RESULTS: Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p = .015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established. CONCLUSIONS: High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.
- MeSH
- cytokiny krev MeSH
- dospělí MeSH
- ELISA MeSH
- GPI-vázané proteiny krev MeSH
- kohortové studie MeSH
- lektiny krev MeSH
- lidé MeSH
- neparametrická statistika MeSH
- novorozenec MeSH
- polymorfismus genetický MeSH
- porod v termínu * MeSH
- předčasný odtok plodové vody krev genetika MeSH
- předčasný porod krev genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- akutní nemoc MeSH
- biologické markery krev MeSH
- cirkulující mikroRNA * krev MeSH
- infarkt myokardu s elevacemi ST úseků patofyziologie MeSH
- kardiogenní šok * patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus MeSH
- prognóza MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Stroke is devastating cerebrovascular event which is responsible for 6.7 million deaths each year worldwide. Inflammation plays an important role in the pathophysiology of stroke. Targeting inflammation after stroke is highly actual topic for both experimental and clinical research. METHODS: Research articles related to cholinergic anti-inflammatory pathway (CHAIP) and stroke were reviewed. The first part of review describes the basic characteristics of inflammatory response after stroke, main components and function of CHAIP. The second part reviews studies focused on CHAIP as a therapeutic target for ischemic and hemorrhagic stroke. Both pharmacological stimulation of α7 nAChR and vagus nerve stimulation after stroke are reviewed. RESULTS: Cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism by which central nervous system regulates immune response and controls inflammation. Vagus nerve, spleen and α7 nicotinic acetylcholine receptor (α7 nAChR) are the main components of CHAIP. CONCLUSION: Targeting cholinergic anti-inflammatory pathway is a promising way of immunomodulation which attenuates inflammation in a complex manner without causing immunosuppression.
- MeSH
- alfa7 nikotinové acetylcholinové receptory fyziologie MeSH
- centrální nervový systém fyziologie MeSH
- cévní mozková příhoda imunologie patofyziologie MeSH
- lidé MeSH
- nervus vagus fyziologie MeSH
- slezina fyziologie MeSH
- zánět patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.
- MeSH
- alely MeSH
- dospělí MeSH
- infarkt myokardu s elevacemi ST úseků diagnóza genetika MeSH
- koronární angioplastika MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 1 genetika MeSH
- matrixová metaloproteinasa 13 genetika MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- polymorfismus genetický MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- tkáňové inhibitory metaloproteinas genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). DESIGN: Prospective observational cohort study. SETTING: One university/tertiary centre. PARTICIPANTS: A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. OUTCOMES: PRIMARY OUTCOME: 1-year mortality. SECONDARY OUTCOMES: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. STATISTICAL METHODS: Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). RESULTS: The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%. CONCLUSIONS: The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.
- MeSH
- biologické markery krev MeSH
- elektrokardiografie * MeSH
- infarkt myokardu krev diagnóza mortalita MeSH
- koronární angioplastika * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokaliny krev MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- natriuretický peptid typu B krev MeSH
- pooperační období MeSH
- prognóza MeSH
- prospektivní studie MeSH
- proteiny akutní fáze MeSH
- protoonkogenní proteiny krev MeSH
- ROC křivka MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.
- MeSH
- analýza přežití MeSH
- biologické markery krev MeSH
- chemokin CCL5 krev genetika MeSH
- dospělí MeSH
- infarkt myokardu krev genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- kardiogenní šok krev genetika patologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci MeSH
- promotorové oblasti (genetika) * MeSH
- senioři MeSH
- srdeční selhání genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
