Biomarkers For Acute Ischemic Stroke Research Articles

Multicenter Validation of lncRNA and Target mRNA Diagnostic and Prognostic Biomarkers of Acute Ischemic Stroke From Peripheral Blood Leukocytes.

Long noncoding RNA (lncRNA) and mRNA profiles in leukocytes have shown potential as biomarkers for acute ischemic stroke (AIS). This study aimed to identify altered lncRNA and target mRNA profiles in peripheral blood leukocytes as biomarkers and to assess the diagnostic value and association with AIS prognosis. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed target mRNAs (DEmRNAs) were screened by RNA sequencing in the discovery set, which consisted of 10 patients with AIS and 20 controls. Validation sets consisted of a multicenter (311 AIS versus 303 controls) and a nested case-control study (351 AIS versus 352 controls). The discriminative value of DElncRNAs and DEmRNAs added to the traditional risk factors was estimated with the area under the curve. NAMPT-AS, FARP1-AS1, FTH1, and NAMPT were identified in the multicenter case-control study (P<0.05). LncRNA NAMPT-AS was associated with cis-target mRNA NAMPT and trans-target mRNA FTH1 in all validation sets (P<0.001). Similarly, AIS cases exhibited upregulated lncRNA FARP-AS1 and FTH1 expression (P<0.001) in the nested case-control study (P<0.001). Furthermore, lncRNA FARP1-AS1 expression was upregulated in AIS patients at discharge with an unfavorable outcome (P<0.001). Positive correlations were found between NAMPT expression level and NIHSS scores of AIS patients (P<0.05). Adding 2 lncRNAs and 2 target mRNAs to the traditional risk factor model improved area under the curve by 22.8% and 5.2% in the multicenter and the nested case-control studies, respectively. lncRNA NAMPT-AS and FARP1-AS1 have potential as diagnostic biomarkers for AIS and exhibit good performance when combined with target mRNA NAMPT and FTH1.

Serum Caspase-3 Levels as a Predictive Molecular Biomarker for Acute Ischemic Stroke.

Caspases are key players in the apoptotic process and have been found to contribute to the pathogenesis of a variety of diseases, including neurological disorders such as ischemic stroke. This study aimed to investigate the serum levels of Caspase-3 in patients with acute ischemic stroke (AIS) and in control patients without ischemic events. Moreover, we explored any potential associations with the clinical outcomes of AIS. We enrolled 69 consecutive patients with clinical signs and symptoms of AIS in the presence of a negative CT scan who presented themselves at the Clinical Neurological Department from the Emergency Clinical Hospital of Galati within the first 24 h of symptom onset. The control group comprised 68 patients without cerebral ischemic pathologies. A comparison of the two groups showed significantly higher levels of caspase-3 at 24 and 48 h after hospital admission. No significant associations between caspase-3 levels and clinical features of AIS were seen. However, in a subgroup analysis conducted on patients with moderate/severe and severe stroke, lower levels of caspase-3 were associated with early mortality. Caspase-3 levels did not directly correlate with AIS severity or prognosis when considering all AIS patients. In patients with moderate to severe National Institute of Health Stroke Scale (NIHSS) scores, caspase-3 might be a prognostic indicator of early death. Further studies are required to confirm these results and further explore the mechanisms behind these findings.

Role of Von Willebrand factor level as a biomarker in acute ischemic stroke

BackgroundVon Willebrand factor (VWF) is a large, multimeric glycoprotein that plays a role in thrombus formation; it is also an important mediator of inflammation. Our study aims to determine the association of VWF plasma level and acute ischemic stroke and determine plasma level of VWF in different subtypes of acute ischemic stroke. This case–control study was conducted on 90 subjects: 30 acute ischemic atherosclerotic stroke patients, 30 acute cardioembolic stroke patients and 30 healthy age and sex-matched control subjects. Stroke patients were recruited within the first week of stroke onset with an age range from 18 to 75 years. All subjects underwent complete neurological examination, duplex ultrasonography (U/S), CT brain, routine laboratory work-up and serum level of VWF.ResultsVWF serum levels were significantly elevated in patients of acute ischemic stroke, compared to control subjects. Higher plasma levels of VWF were observed in patients with acute ischemic atherosclerotic stroke.ConclusionSerum level of VWF can be used as a marker for acute ischemic stroke, especially the atherosclerotic subtype.

Brain-Derived Exosomal CircRNAs in Plasma Serve as Diagnostic Biomarkers for Acute Ischemic Stroke.

Acute ischemic stroke (AIS), commonly known as stroke, is a debilitating condition characterized by the interruption of blood flow to the brain, resulting in tissue damage and neurological deficits. Early diagnosis is crucial for effective intervention and management, as timely treatment can significantly improve patient outcomes. Therefore, novel methods for the early diagnosis of AIS are urgently needed. Several studies have shown that bioactive molecules contained in extracellular vesicles, especially circRNAs, could be ideal markers for the diagnosis of many diseases. However, studies on the effects of exosomes and their circRNAs on the development and prognosis of AIS have not been reported extensively. Therefore, we explored the feasibility of using circRNAs in plasma brain-derived exosomes as biomarkers for AIS. By high-throughput sequencing, we first identified 358 dysregulated circRNAs (including 23 significantly upregulated circRNAs and 335 significantly downregulated circRNAs) in the plasma brain-derived exosomes of the brain infarct patient group compared to those of the noninfarct control group. Five upregulated circRNAs (hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808, and hsa_circ_0000097) were selected for further validation via Real-Time Quantitative Reverse Transcription PCR (qRT‒PCR) in a larger cohort based on the exclusion criteria of log2FC > 1, p < 0.05 and measurable expression. We found that the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were significantly upregulated in AIS patients and could serve as potential biomarkers for AIS with high specificity and sensitivity. Moreover, the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were also found to be positively correlated with National Institutes of Health Stroke Scale (NISS) and modified Rankin scale (mRS) scores, which indicated that the presence of these circRNAs in plasma brain-derived exosomes could also determine the progression of AIS.

The Role of microRNAs as Super-early Biomarkers in Acute Ischemic Stroke: Preliminary Data Analysis of a Systematic Review (P10-5.002)

The Role of microRNAs as Super-early Biomarkers in Acute Ischemic Stroke: Preliminary Data Analysis of a Systematic Review (P10-5.002)

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

Prognostic Neuroimaging Biomarkers in Acute Vascular Brain Injury and Traumatic Brain Injury.

Prognostic imaging biomarkers after acute brain injury inform treatment decisions, track the progression of intracranial injury, and can be used in shared decision-making processes with families. Herein, key established biomarkers and prognostic scoring systems are surveyed in the literature, and their applications in clinical practice and clinical trials are discussed. Biomarkers in acute ischemic stroke include computed tomography (CT) hypodensity scoring, diffusion-weighted lesion volume, and core infarct size on perfusion imaging. Intracerebral hemorrhage biomarkers include hemorrhage volume, expansion, and location. Aneurysmal subarachnoid biomarkers include hemorrhage grading, presence of diffusion-restricting lesions, and acute hydrocephalus. Traumatic brain injury CT scoring systems, contusion expansion, and diffuse axonal injury grading are reviewed. Emerging biomarkers including white matter disease scoring, diffusion tensor imaging, and the automated calculation of scoring systems and volumetrics are discussed.

Inflammation biomarkers in acute ischemic stroke according to different etiologies.

High throughput technologies provide new opportunities to further investigate the pathophysiology of ischemic strokes. The present cross-sectional study aimed to evaluate potential associations between the etiologic subtypes of ischemic stroke and blood-based proteins. We investigated the associations between ischemic stroke subtypes and a panel of circulating inflammation biomarkers in 364 patients included in the Stroke Cohort Augsburg (SCHANA). Stroke etiologies were categorized according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Serum concentrations of 52 biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel, ICAM-1 set and VCAM-1 set, plus the Pro™ Human TH17 cytokine sCD40L set and IL31 set (all Bio-Rad, USA). Multivariable linear regression models were used to examine associations. Point estimates were calculated as the mean difference in -standardized cytokine levels on the log2 -scale. Stromal-cell-derived-factor 1 alpha (SDF-1a) showed significantly higher serum levels in cardioembolic compared with large vessel atherosclerotic stroke (β = 0.48; 95% CI 0.22; 0.75; Padj = 0.036). Significantly lower levels of interleukin-6 (IL-6) (β = -0.53; 95% CI -0.84; -0.23; Padj = 0.036) and macrophage migration inhibitory factor (MIF) (β = -0.52; 95% CI -0.84; -0.21; Padj = 0.043) were found in the small vessel versus large vessel stroke subtype. Immune dysregulations observed in different stroke subtypes might help uncover pathophysiological mechanisms of the disease. Further studies are needed to validate identified biomarkers in diverse study populations before they can potentially be used in clinical practice to further improve stroke management and patient outcomes.

The expression levels of circulating miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in acute ischemic stroke.

Plasma miRNAs can characterize several diseases, including acute ischemic stroke (AIS), which is noninvasive and currently affordable in most laboratories worldwide. We aimed to demonstrate plasma miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in AIS.GSE110993 and GSE86291 datasets were analyzed to obtain plasma differentially expressed miRNAs between AIS and healthy control subjects (HCs). We further applied RT-qPCR for the validation in 85 AIS patients and 85 HCs. Receiver operating characteristic (ROC) curve were conducted to evaluate their diagnostic utility in AIS. Correlation was analyzed between DEmiRNAs and clinical and laboratory parameters, as well as inflammatory markers. The plasma levels of miR-140-3p, miR-130a-3p, and miR-320b were found to be consistently altered in both GSE110993 and GSE86291 datasets. In comparison to HCs, AIS patients at admission exhibited lower levels of miR-140-3p and miR-320b and higher level of miR-130a-3p in their plasma. The ROC analysis revealed that plasma miR-140-3p, miR-130a-3p, and miR-320b had area under the curve values of 0.790, 0.831, and 0.907, respectively. When combined, these miRNAs showed superior discriminatory power with a sensitivity of 91.76% and specificity of 95.29%. Plasma miR-140-3p and miR-320b negatively correlated glucose levels and inflammatory markers (IL-6, MMP-2, MMP-9, and VEGF) in AIS patients. Conversely, plasma miR-130a-3p levels were positively associated with glucose levels and these markers. Plasma miR-140-3p, miR-130a-3p, and miR-320b levels varied significantly among AIS patients with different NIHSS scores. Plasma miR-140-3p, miR-130a-3p, and miR-320b had high diagnostic value in AIS patients, which were correlated with inflammation and severity in stroke.

The potential role of micro-RNA 125b-5p level in predicting outcome from thrombolytic therapy in patients with acute ischemic stroke

Several studies highlighted a significant role of specific miRNA as diagnostic and prognostic biomarkers for acute ischemic stroke. The aim of this work was to study micro-RNA 125b-5p level in patients with acute ischemic stroke in relation to stroke etiology, risk factors, severity and outcome. This case–control study was conducted on 40 patients with acute ischemic stroke eligible for receiving rt-PA and 40 age and sex matched healthy controls, Patients were submitted to neurological and radiological assessment. Functional outcome after 3 months was assessed using the modified Rankin Scale (mRS). Plasma micro-RNA 125b-5p levels were measured for both patients and control groups by quantitative real time PCR. MiRNA-125b-5p was extracted from the plasma samples then Real-time quantitative reversed transcription PCR (RT-qPCR) analysis was done. To analyze miRNA-125b-5p expression in plasma, the ∆Cq value of miRNA-125b-5p was calculated by subtracting Cq of miRNA-125b-5p from the average Cq of MiRNA RNU6B. Stroke patients had significantly higher circulating micro-RNA 125b-5p levels in comparison to healthy controls (P value = 0.01). The circulating levels of micro-RNA 125b-5p were positively correlated with stroke severity assessed by National Institutes of Health Stroke Scale (NIHSS) and infarction size. Stroke patients with poor outcome had significantly higher circulating levels of micro-RNA 125b-5p in comparison to those with good outcome (P value ≤ 0.001). The circulating levels of micro-RNA 125b-5p were significantly higher in patients who developed complications after receiving rt-PA (P value ≤ 0.001). Logistic regression model revealed that each unit increase in micro-RNA125b-5p decreased the odds of good outcome by 0.095 (95% CI 0.016–0.58, P value = 0.011). Plasma micro-RNA 125b-5p is significantly elevated is ischemic stroke patients. It is positively correlated with stroke severity and strongly associated with poor outcome and complications after thrombolytic therapy.

Clinical Application of Circular RNAs as Biomarkers in Acute Ischemic Stroke.

Despite the substantial improvement in diagnosis and treatment within the last decades, ischemic stroke still represents a challenge, responsible still for a high burden of morbidity and mortality. Among the unmet clinical needs are the difficulties in identifying those subjects with the greatest risk of developing a stroke, the challenges in obtaining a timely diagnosis, the prompt recognition of the different clinical forms of stroke, the assessment of the response to treatments and the prognostic assessment. All these issues might be improved with appropriate smart biomarkers that could better inform clinical management. The present article offers an overview of the potential role of circular RNAs as disease biomarkers in stroke. A systematic approach was adopted to gather all potentially relevant information in order to provide a panoramic view on this class of promising molecules.

Quantitative analysis of cell-free plasma DNA as a prognostic biomarker in acute ischemic stroke patients

BackgroundStroke has become a leading cause of death and disability worldwide, and despite the introduction of new screening programs, therapies, and monitoring technologies, there is still a need to develop more useful biochemical tests to monitor treatment response and inform clinical decision-making. Cell-free DNA released from damaged neurons in stroke patients may be useful in assessing stroke prognosis. The purpose of this study was to evaluate the role of cell-free DNA and a highly sensitive blood biomarker in acute ischemic stroke. 188 patients with acute ischemic stroke were recruited for the study. The level of cell-free DNA in plasma was estimated using a real-time PCR assay for the β-globin gene (Qiagen-Rotor-Gene Q MDX, Germany). Clinical assessment was performed with the National Institutes of Health Stroke Scale (NIHSS) at the time of admission. After a period of three months from the onset of stroke, (mRS) scores were estimated using the modified Rankin scale.ResultsElevated levels of cell-free DNA were found in patients with higher NIHSS admission scores and mRS 3-month scores (p < 0.05). The regression analysis revealed that the markers are associated with an unfavorable outcome in comparison to other stroke risk factors (R2 = 0.224). Stroke outcome was relatively better in patients with a cell-free DNA level < 10,000 kilogenome equivalents/L (p < 0.05).ConclusionsMeasurement of total cell-free DNA levels is a simpler and less-expensive biomarker suggesting potential clinical application of blood-based test. Cell-free DNA can contribute to the clinical evaluation and optimal management of ischemic stroke patients. This biomarker seems to have the potential to predict the long-term prognosis of acute ischemic stroke.

Circular RNA as biomarkers for acute ischemic stroke: Asystematic review and meta-analysis.

Rapid diagnosis of acute ischemic stroke (AIS) patients is still challenging, and reliable biomarkers are needed. Noncoding RNAs are important for many physiological activities, among which circular RNAs (circRNAs) have been proven to be more tissue-specific and conservative. Many recent studies found the potential of circRNAs as biomarkers for many diseases, including cardiovascular diseases, cancers, and ischemic stroke. This systemic review and meta-analysis aimed to identify circRNAs as potential biomarkers for AIS. This study has been prospectively registered in PROSPERO (Registration No. 11 CRD42021288033). Published literature comparing circRNA expression profiles between AIS and non-AIS in human and animal models were retrieved from the articles published by January 2023 in major databases. We descriptively summarized the included studies, conducted meta-analysis under a random effects model, and did bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Totally 23 studies were included, reporting 18 distinctive upregulated and 20 distinctive downregulated circRNAs. Diagnostic meta-analysis indicated discriminative ability of the circRNAs. Furthermore, circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1 were reported with the same regulation trend in more than one study (animal studies included). GO and KEGG enrichment analyses indicated that the target genes of these five circRNAs were enriched in regulating cell proliferation, apoptosis, and oxidative stress. This study demonstrates that circRNAs (circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1) generally are promising as potential biomarkers for AIS. However, due to the limited number of studies, diagnostic value of individual circRNA could not be validated. More in vitro and in vivo functional studies are needed.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus

BackgroundHyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior...

Abstract TP226: Impact Of Apolipoprotein A-i In The Attenuation Of Stroke And Stroke Symptoms

Apolipoprotein AI is the major protein component of high-density lipoprotein (HDL) particles in plasma. Inflammatory cytokines such as TNF and IL-1β repress the production of ApoA-I from hepatocytes and increase the expression of serum amyloid A (SAA), which becomes the major protein component of HDL in this context. Consequently, lipid-poor ApoA-I is rapidly catabolized in the liver and the kidney. These findings could be meaningful if ApoA-I, in addition to its proimmune features, had anti-inflammatory potential. In this way, removal of ApoA-I could intensify the inflammatory response, resulting in a more robust effect. Recent studies have suggested that serum apolipoprotein A1 maybe a predictor and prognostic biomarker in acute ischemic stroke in humans. To understand the impact of ApoA-I in stroke, we have begun to analyze the role of ApoA-I in mouse models of stroke. Mice with reduced or deficient in ApoA-I and subjected to ischemia and reperfusion injury or permanent ischemia, had increased inflammatory responses, larger infarct volumes, and poorer outcomes than wildtype mice. Mice transgenic for the human ApoA-I gene showed a level of protection not seen in the wildtype mice when given an ischemic injury. Administration of AAV human ApoA-I increased HDL levels in deficient mice and provided protection against ischemic injury. Additionally, drugs to enhance ApoA-I expression showed protection against strokes in the mouse models. These studies, along with subsequent investigations will provide a better understanding and potential therapeutic approaches in the field of stroke.

Radiomics Analysis of Diffusion-Weighted Imaging and Long-Term Unfavorable Outcomes Risk for Acute Stroke.

Diffusion-weighted imaging radiomics could be used as prognostic biomarkers in acute ischemic stroke. We aimed to identify a clinical and diffusion-weighted imaging radiomics model for individual unfavorable outcomes risk assessment in acute ischemic stroke. A total of 1716 patients with acute ischemic stroke from 2 centers were divided into a training cohort and a validation cohort. Patient outcomes were measured with the modified Rankin Scale score. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2. The primary end point was all-cause mortality or outcomes 1 year after stroke. The MRI-DRAGON score was calculated based on previous publications. We extracted and selected the infarct features on diffusion-weighted imaging to construct a radiomic signature. The clinic-radiomics signature was built by measuring the Cox proportional risk regression score (CrrScore) and compared with the MRI-DRAGON score and the ClinicScore. CrrScore model performance was estimated by 1-year unfavorable outcomes prediction. A high radiomic signature predicted a higher probability of unfavorable outcomes than a low radiomic signature in the training (hazard ratio, 3.19 [95% CI, 2.51-4.05]; P<0.0001) and validation (hazard ratio, 3.25 [95% CI, 2.20-4.80]; P<0.0001) cohorts. The diffusion-weighted imaging Alberta Stroke Program Early CT Score, age, glucose level before therapy, National Institutes of Health Stroke Scale score on admission, glycated hemoglobin' radiomic signature, hemorrhagic infarction, and malignant cerebral edema were associated with an unfavorable outcomes risk after multivariable adjustment. A CrrScore nomogram was developed to predict outcomes and had the best performance in the training (area under the curve, 0.862) and validation cohorts (area under the curve, 0.858). The CrrScore model time-dependent areas under the curve of the probability of unfavorable outcomes at 1 year in the training and validation cohorts were 0.811 and 0.801, respectively. The CrrScore model allows the accurate prediction of patients with acute ischemic stroke outcomes and can potentially guide rehabilitation therapies for patients with different risks of unfavorable outcomes.

NR-2 antikor peptid düzeyinin akut iskemik inmede tanı, prognoz ve koma skorları ile ilişkisi var mıdır?

Aim: This study aimed to demonstrate the diagnostic and prognostic value of NR-2 peptides as a biomarker in acute ischemic stroke and to evaluate their correlation with the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS).Materials and Methods: The importance of NR-2 peptide level in diagnosis and prognosis in acute stroke was investigated cross-sectional and prospectively. The study included 101 patients, who presented to a tertiary healthcare facility and were diagnosed with acute stroke, and 57 healthy controls. In the whole study population, serum NR-2 peptide levels were measured using the ELISA method.Results: The NR-2 peptide level was 6.32 ± 8.30 in the patient group and 3.91 ± 1.64 in the study group. The NR-2 peptide level was significantly higher in the patient group (p = 0.006). No correlation was detected between NR-2 peptide levels and scores in the GCS or NIHSS. The results indicated that NR-2 was a potential biomarker elevated in the early phase of acute stroke, but had no correlation with the prognosis of acute stroke.Conclusion: Although our data shed light on the use of the NR-2 peptide level as a biomarker in the acute phase in patients with stroke, data are insufficient to predict prognosis. We think that larger, multicenter studies with longer follow-up periods are needed.

Construction of circRNA-Mediated Immune-Related ceRNA Network and Identification of Circulating circRNAs as Diagnostic Biomarkers in Acute Ischemic Stroke.

Background and PurposeAccumulating evidence suggests that circular RNAs (circRNAs) are involved in immune and inflammatory processes after acute ischemic stroke (AIS). However, the roles of circRNA-mediated competing endogenous RNA (ceRNA) in modulating immune inflammation of AIS have not yet been determined. This study aimed to construct a circRNA-mediated immune-related ceRNA network and identify novel circRNAs in AIS.MethodsMicroarray data were downloaded from the GEO database and further analysed by R software. Then, we constructed a circRNA-mediated ceRNA network based on interaction information from the bioinformatics database. A topological property analysis of the ceRNA network was conducted to screen novel circRNAs. Finally, we further applied quantitative real-time polymerase chain reaction (qRT-PCR) to two independent sets.ResultsWe constructed an AIS immune-related ceRNA (AISIRC) network containing immune-related genes (IRGs), miRNAs, and circRNAs. Additionally, we extracted the subnetwork from the AISIRC network and screened six immune-related circRNAs. After identification and validation, we finally confirmed that plasma levels of circPTP4A2 and circTLK2 were significantly increased in AIS patients compared with both healthy control subjects (HCs) and transient ischemic attack (TIA) patients. Logistic regression and receiver-operating characteristic (ROC) curve analyses demonstrated that these two circRNAs may function as predictive and discriminative biomarkers for AIS. We also confirmed that plasma levels of circPTP4A2 were elevated in TIA patients compared with HCs and might be an independent risk factor for predicting TIA. Longitudinal analysis of circRNA expression up to 90 days after AIS indicated that the ability of circPTP4A2 and circTLK2 to monitor AIS dynamics was highly desirable.ConclusionIn summary, the circRNA-mediated immune-related ceRNA network was successfully constructed, and two circulating circRNAs (circPTP4A2 and circTLK2) improved sensitivity for the diagnosis of AIS and could be considered diagnostic biomarkers.

The Relationship Between the Fibrinogen to Albumin Ratio and Early Outcomes in Patients with Acute Pontine Infarction.

Background and purposePrevious studies have indicated that fibrinogen and low serum albumin levels are associated with poor outcomes of acute ischemic stroke. The role of the fibrinogen-to-albumin ratio (FAR) as a novel inflammatory and thrombotic biomarker in acute ischemic stroke is unclear. This study aims to investigate the relationship between the FAR and 3-month outcomes of acute pontine infarction. Methods: Patients with acute pontine infarction were consecutively included. All patients were followed up at 3 months after onset, and the 3-month outcome was evaluated using modified Rankin Scale (mRS) scores. A score of 0 to 2 was defined as a good outcome, and a score ≥ 3 was defined as a poor outcome. Receiver operating curve (ROC) analysis was used to calculate the optimal cutoff values for patients with acute pontine infarction. Then, a binary logistic regression model was used to evaluate the risk factors for a poor outcome after acute pontine infarction. Results: A total of 264 patients with acute pontine infarction were included. Eighty (30.3%) patients were included in the poor outcome group. The optimal cutoff value of the FAR for predicting the 3-month outcome of acute pontine infarction was 8.199. The FAR was independently associated with a poor outcome at 3 months in patients with acute pontine infarction (odds ratio [OR] = 1.293, 95% confidence interval [CI]: 1.150-1.453). Conclusions: We found that a high FAR predicted poor 3-month outcomes in patients with acute pontine infarction.

Phenylacetylglutamine, a Novel Biomarker in Acute Ischemic Stroke.

Background: To discover novel metabolic biomarkers of ischemic stroke (IS), we carried out a two-stage metabolomic profiling of IS patients and healthy controls using untargeted and targeted metabolomic approaches.Methods: We applied untargeted liquid chromatography-mass spectrometry (LC-MS) to detect the plasma metabolomic profiles of 150 acute IS patients and 50 healthy controls. The candidate differential microbiota-derived metabolite phenylacetylglutamine (PAGln) was validated in 751 patients with IS and 200 healthy controls. We evaluated the associations between PAGln levels and the severity and functional outcomes of patients with IS. Clinical mild stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score 0–5, and moderate-severe stroke as NIHSS score >5. A favorable outcome at 3 months after IS was defined as the modified Rankin Scale (mRS) score 0–2, and unfavorable outcome as mRS score 3–6.Results: In untargeted metabolomic analysis, we detected 120 differential metabolites between patients with IS and healthy controls. Significantly altered metabolic pathways were purine metabolism, TCA cycle, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. Elevated plasma PAGln levels in IS patients, compared with healthy controls, were observed in untargeted LC-MS analysis and confirmed by targeted quantification (median 2.0 vs. 1.0 μmol/L; p < 0.001). Patients with moderate-severe stroke symptoms and unfavorable short-term outcomes also had higher levels of PAGln both in discovery and validation stage. After adjusting for potential confounders, high PAGln levels were independently associated with IS (OR = 3.183, 95% CI 1.671–6.066 for the middle tertile and OR = 9.362, 95% CI 3.797–23.083 for the highest tertile, compared with the lowest tertile) and the risk of unfavorable short-term outcomes (OR = 2.286, 95% CI 1.188–4.401 for the highest tertile).Conclusions: IS patients had higher plasma levels of PAGln than healthy controls. PAGln might be a potential biomarker for IS and unfavorable functional outcomes in patients with IS.