Stroke Biomarkers Research Articles

Plasma symmetric dimethylarginine as a metabolite biomarker of severe acute ischemic stroke

Plasma symmetric dimethylarginine as a metabolite biomarker of severe acute ischemic stroke

Pathogenesis and Biomarkers of Cancer-Related Ischemic Stroke.

To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS. Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)). The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P<0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P<0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P<0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P<0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P<0.05). In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study. Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score, 3-6) at 3 months after ischemic stroke. During 3 months of follow-up, 877 participants experienced the primary outcome. After multivariate adjustment, each 500 ng/mL increase of phenylacetylglutamine was associated with a 7% (P=0.012), 6% (P=0.016), and 6% (P=0.028) increased risk of the primary outcome, major disability, and death, respectively. The odds ratios or hazard ratios in the highest versus the lowest quartile of plasma phenylacetylglutamine were 1.62 ([95% CI, 1.18-2.23]; Ptrend=0.001) for the primary outcome, 1.62 ([95% CI, 1.16-2.24]; Ptrend=0.001) for major disability, and 2.59 ([95% CI, 1.19-5.60]; Ptrend=0.025) for death, respectively. There was a significantly worse shift in the distribution of modified Rankin Scale score at 3 months with higher phenylacetylglutamine quartiles (Ptrend=0.003). Multiple-adjusted spline regression model showed a linear relationship between phenylacetylglutamine and primary outcome (P value for linearity<0.001). The addition of plasma phenylacetylglutamine to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement, 19.34%; P<0.001; integrated discrimination improvement, 0.23%; P=0.019). Elevated plasma phenylacetylglutamine levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that phenylacetylglutamine may be a promising prognostic biomarker for ischemic stroke. Further studies are needed to investigate whether phenylacetylglutamine is a stroke-specific biomarker.

Enhanced Stability of Hairpin-Functionalized DNA Tetrahedral Nanostructures for miRNA Detection in Plasma from Ischemic Stroke Patients

The enzyme-free amplification technique using the Hybridization Chain Reaction (HCR) is gaining traction for its efficiency in miRNA analysis. Conventional HCR (C-HCR) with hairpin probes faces challenges due to enzymatic degradation in body fluids, leading to potential false-positive results. This study addresses the critical need for a more reliable method that resists enzymatic breakdown and improves diagnostic accuracy for detecting miRNA related to ischemic stroke. We have developed a novel DNA tetrahedral nanostructures-mediated HCR (DTN-HCR) platform for the precise detection of microRNA-25 (miR-25), a biomarker for ischemic stroke. Incorporating two unique DNA tetrahedral nanostructures with embedded hairpin structures (DTN-HP1 and DTN-HP2), this platform activates upon miR-25 binding, initiating a robust DTN-HCR reaction. This reaction forms extensive DNA tetrahedron clusters that significantly boost the fluorescence signal, enabling detection thresholds as low as 5.4 pM. The method showcases exceptional specificity by distinguishing target miRNA from close analogues and maintains structural integrity against DNase I and fetal bovine serum (FBS), verified through polyacrylamide gel electrophoresis (PAGE). It successfully differentiates ischemic stroke patients from healthy controls by analyzing peripheral blood-derived miRNAs. This study concludes that the DTN-HCR platform substantially enhances the specificity and stability of miRNA detection, marking a significant advancement in non-enzymatic miRNA analysis techniques. With its capability to accurately identify ischemic stroke biomarkers at very low concentrations and its resistance to enzymatic degradation, the DTN-HCR method presents a valuable diagnostic tool for ischemic stroke, potentially improving early detection and monitoring in a clinical environment.

Endothelial and circulating progenitor cells as prognostic biomarkers of stroke: A systematic review and meta-analysis

Endothelial and circulating progenitor cells as prognostic biomarkers of stroke: A systematic review and meta-analysis

Exploring common biomarkers of ischemic stroke and obstructive sleep apnea through bioinformatics analysis.

Clinical observations have shown that many patients with ischemic stroke (IS) have a history of obstructive sleep apnea (OSA) both before and after the stroke's onset, suggesting potential underlying connections and shared comorbid mechanisms between the two conditions. The aim of this study is to identify the genetic characteristics of OSA patients who develop IS and to establish a reliable disease diagnostic model to assess the risk of IS in OSA patients. We selected IS and OSA datasets from the Gene Expression Omnibus (GEO) database as training sets. Core genes were identified using the Limma package, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning algorithms. Gene Set Variation Analysis (GSVA) was conducted for pathway enrichment analysis, while single-sample gene set enrichment analysis (ssGSEA) was employed for immune infiltration analysis. Finally, a diagnostic model was developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, with its diagnostic efficacy validated using receiver operating characteristic (ROC) curves across two independent validation sets. The results revealed that differential analysis and machine learning identified two common genes, TM9SF2 and CCL8, shared between IS and OSA. Additionally, seven signaling pathways were found to be commonly upregulated in both conditions. Immune infiltration analysis demonstrated a significant decrease in monocyte levels, with TM9SF2 showing a negative correlation and CCL8 showing a positive correlation with monocytes. The diagnostic model we developed exhibited excellent predictive value in the validation set. In summary, two immune-related core genes, TM9SF2 and CCL8, were identified as common to both IS and OSA. The diagnostic model developed based on these genes may be used to predict the risk of IS in OSA patients.

Proteomic and genomic evaluation of plasma protein biomarkers for atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a common arrhythmia and an important cause of ischemic stroke. Several plasma proteins have been suggested as biomarkers for the risk of AF and subsequent stroke in previous studies, but validation in independent cohorts is needed. Large-scale integration of proteomics with genetic and clinical data holds potential for refinement of disease prediction and risk stratification. Purpose This study aimed to evaluate previously suggested plasma protein biomarkers of AF and ischemic stroke using plasma protein measurements in a large cohort. Methods Ten tentative protein biomarkers previously associated with AF or ischemic stroke in AF patients, were evaluated in a nested case-control study comprising 49,757 individuals from the UK biobank (UKB). Plasma proteins were measured by normalized protein expression on the Olink platform. Outcomes were incident AF and ischemic stroke. The proteins were evaluated in Cox regression models adjusted for sex, age, and clinical risk factors. To assess whether the proteins were independent predictors, they were evaluated in sensitivity analyses with additional adjustment for NT-proBNP levels. Polygenic risk scores were calculated for plasma protein concentrations using the PRS-CS-auto algorithm and tested for association with AF or ischemic stroke in an independent subset of the UKB cohort without plasma protein measurements (n=379,392). Results All ten plasma proteins were associated with incident AF in the primary model, and eight were associated with incident ischemic stroke (P-values &amp;lt; 0.0025 for all). Adjusted for NT-proBNP levels, the proteins interleukin-6, GDF15, angiopoietin 2, and Troponin-I remained independently associated with AF, and the proteins GDF15, Cystatin-C, interleukin-6, ADAMTS13, and FGF23 remained independently associated with ischemic stroke. Polygenic risk scores for NT-proBNP and angiopoietin 2 were associated with increased rates of AF. No polygenic scores were significantly associated with ischemic stroke. Conclusion Large-scale proteomic evaluation validated ten plasma proteins associated AF and found eight to be associated with ischemic stroke. Seven proteins were associated with AF or ischemic stroke independently of NT-proBNP levels. Additional genomic evaluation provided evidence of associations between incident AF and genetically predicted plasma levels of angiopoietin 2 and NT-proBNP. As proteomic analyses of the plasma proteome become cheaper and more readily available, these findings could contribute to future risk stratification and selection of individuals for AF screening programs.Proteins associated with AFProteins associated with ischemic stroke

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

Transfer RNAs are Linked to Ischemic Stroke and Major Bleeding in Patients with End-Stage Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for the false discovery rate (FDR). No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case-control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared with controls (FDR < 0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding. While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.

Current Trends in Stroke Biomarkers: The Prognostic Role of S100B and GFAP

Stroke is the third leading cause of death in the developed world and a major cause of chronic disability, especially among the elderly population. The major biomarkers of stroke which are the most promising for predicting onset time and independently differentiating ischemic from hemorrhagic and other stroke subtypes are at present limited to a few. This review aims to emphasize on the prognostic role of S100 calcium-binding protein b (S100B), and Glial Fibrillary Acidic Protein (GFAP) in patients with stroke. An electronic search of the published research from January 2000 to February 2024 was conducted using the MEDLINE, Scopus, and Cochrane databases. The implementation of S100B and GFAP in existing clinical scales and imaging modalities may be used to improve diagnostic accuracy and realize the potential of blood biomarkers in clinical practice. The reviewed studies highlight the potential of S100B and GFAP as significant biomarkers in the prognosis and diagnosis of patients with stroke and their ability of predicting long-term neurological deficits. They demonstrate high sensitivity and specificity in differentiating between ischemic and hemorrhagic stroke and they correlate well with stroke severity and outcomes. Several studies also emphasize on the early elevation of these biomarkers post-stroke onset, underscoring their value in early diagnosis and risk stratification. The ongoing research in this field should aim at improving patient outcomes and reducing stroke-related morbidity and mortality by developing a reliable, non-invasive diagnostic tool that can be easily implemented in several healthcare settings, with the ultimate goal of improving stroke management.

Association between the serum glucose-to-potassium ratio and clinical outcomes in ischemic stroke patients after endovascular thrombectomy.

The baseline glucose-to-potassium ratio (GPR) is associated with poor outcomes in patients with acute brain injury and intracranial hemorrhage. However, the impact of serum GPR on clinical outcomes after endovascular thrombectomy (EVT) is unclear. This study aimed to evaluate the association between the GPR at admission and functional outcomes at 90 days after EVT. We retrospectively reviewed our database for patients with acute ischemic stroke involving an anterior circulation large-vessel occlusion who received EVT between October 2019 and December 2021. The baseline serum GPR was measured after admission. The primary outcome was a 90-day poor outcome, which was defined as a modified Rankin scale score of 3-6. A total of 273 patients (mean age, 70.9 ± 11.9 years; 161 men) were finally included for analyses. During the 90-day follow-up, 151 patients (55.3%) experienced an unfavorable outcome. After adjusting for demographic characteristics and other potential confounders, the increased GPR was significantly associated with a higher risk of a 90-day poor outcome (odds ratio, 1.852; 95% confidence interval, 1.276-2.688, p = 0.001). Similar results were observed when the GPR was analyzed as a categorical variable. In addition, the restricted cubic spline observed a positive and linear association between the GPR and poor outcomes at 90 days (p = 0.329 for linearity; p = 0.001 for linearity). Our study found that ischemic stroke patients with the higher GPR at admission were more likely to have an unfavorable prognosis at 3 months, suggesting that GPR may be a potential prognostic biomarker for ischemic stroke after EVT.

Combined Analysis of Human and Experimental Rat Samples Identified Biomarkers for Ischemic Stroke.

The genetic transcription profile and underlying molecular mechanisms of ischemic stroke (IS) remain elusive. To address this issue, four mRNA and one miRNA expression profile of rats with middle cerebral artery occlusion (MCAO) were acquired from the Gene Expression Omnibus (GEO) database. A total of 780 differentially expressed genes (DEGs) and 56 miRNAs (DEMs) were screened. Gene set and functional enrichment analysis revealed that a substantial number of immune-inflammation-related pathways were abnormally activated in IS. Through weighted gene co-expression network analysis, the turquoise module was identified as meaningful. By taking the intersection of the turquoise module genes, DEM-target genes, and all DEGs, 354 genes were subsequently obtained as key IS-related genes. Among them, six characteristic genes were identified using the least absolute shrinkage and selection operator. After validation with three external datasets, transforming growth factor beta 1 (Tgfb1) was selected as the hub gene. This finding was further confirmed by gene expression pattern analysis in both the MCAO model rats and clinical IS patients. Moreover, the expression of the hub genes exhibited a negative correlation with the modified Rankin scale score (P < 0.05). Collectively, these results expand our knowledge of the genetic profile and molecular mechanisms involved in IS and suggest that the Tgfb1 gene is a potential biomarker of this disease.

Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study.

Background: Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. Methods: We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. Results: Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5-5.0] ng/mL; n = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3-4.2] ng/mL; n = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. Conclusions: Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology.

Influence of Anticoagulants and Heparin Contaminants on the Suitability of MMP-9 as a Blood-Derived Biomarker.

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9.

Intracranial aneurysm stiffness assessment using 4D Flow MRI

BackgroundAlthough arterial stiffness is known as a biomarker for cardiovascular events and stroke, there is limited information in the literature regarding the stiffness of intracranial aneurysms. In this study, we aim to assess the stiffness of intracranial aneurysms using 4D Flow MRI. MethodsA total of 27 aneurysms in 25 patients with internal carotid artery aneurysms were included in this study. Using 4D Flow MRI, we measured the arterial pulse wave form during a cardiac cycle at planes proximal and distal to the target aneurysm. The damping of these waveforms through the aneurysm was defined as the aneurysm damping index (ADI) and compared to the contralateral side. We also investigated the clinical factors related to the ADI. ResultsADI assessment was successful in all cases. The average ADI was 1.18±0.28, which was significantly larger than 1.0 (P = 0.0027 [t-test]). The ADI on the aneurysm side was larger than on the contralateral side (1.19±0.30 vs 1.05±0.17, P = 0.029 [t-test]). On multivariate analysis, the use of beta-blockers (β=0.46, P = 0.015) and smoking history (β=-0.22, P = 0.024) showed a significant correlation with ADI. ConclusionWe have proposed a novel method to observe arterial pulse wave dumping through intracranial aneurysm using 4D Flow MRI. The damping can be quantitatively observed, and the ADI has correlations with clinical factors such as antihypertensive drugs and smoking. Further studies should focus more on evaluating aneurysm stiffness and its clinical applications.

An intelligent fluorescence sensing platform based on entropy-driven toehold-mediated strand displacement cycle reaction for point-of-care testing of miRNA

BackgroundMicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications. ResultsIn this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 μM∼10 μ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment. SignificanceIn summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences.

Comprehensive analysis of molecular, physiological, and functional biomarkers of aging with neurological diseases using Mendelian randomization.

An increasing burden of neurological diseases (NDs) has been a public health challenge in an aging society. Age, especially biological age, is the most important risk factor for NDs. Identification of biomarkers of aging to capture NDs might lead to a better understanding of the underlying mechanisms of pathological brain aging and the implementation of effective intervention. We conducted a comprehensive two-sample Mendelian Randomization (MR) study to investigate the association between various biomarkers of aging and three leading causes of NDs: Alzheimer's disease (AD), vascular dementia (VaD), and ischemic stroke. Publicly available GWAS summary statistics on people from European ancestry were obtained for six molecular biomarkers, two physiological biomarkers, and eight functional biomarkers, and three NDs. Genetic variants serving as instrumental variables (IVs) were identified for each biomarker. The MR analysis included inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. We found that short telomere length and decrease in appendicular lean mass were associated with an increased risk for AD (OR IVW = 1.12 per 1SD decrease, 95% confidence interval 1.02-1.22, and OR IVW = 1.11, 1.06-1.16, respectively), whereas high frailty index showed a protective effect for AD. Accelerated BioAge appeared to be associated with increased risk for ischemic stroke (OR IVW = 1.3 per year in BioAge acceleration, 95% CI 1.19-1.41). Our findings implied a causal association of short telomere length and a decrease in appendicular lean mass with an increased risk for AD, while BioAge appeared to be a good biomarker for ischemic stroke. Further studies are needed to validate these associations and explore underlying mechanisms.

Identification of Blood Biomarkers in Ischemic Stroke by Integrated Analysis of Metabolomics and Proteomics.

We aimed to uncover the pathological mechanism of ischemic stroke (IS) using a combined analysis of untargeted metabolomics and proteomics. The serum samples from a discovery set of 44 IS patients and 44 matched controls were analyzed using a specific detection method. The same method was then used to validate metabolites and proteins in the two validation sets: one with 30 IS patients and 30 matched controls, and the other with 50 IS patients and 50 matched controls. A total of 105 and 221 differentially expressed metabolites or proteins were identified, and the association between the two omics was determined in the discovery set. Enrichment analysis of the top 25 metabolites and 25 proteins in the two-way orthogonal partial least-squares with discriminant analysis, which was employed to identify highly correlated biomarkers, highlighted 15 pathways relevant to the pathological process. One metabolite and seven proteins exhibited differences between groups in the validation set. The binary logistic regression model, which included metabolite 2-hydroxyhippuric acid and proteins APOM_O95445, MASP2_O00187, and PRTN3_D6CHE9, achieved an area under the curve of 0.985 (95% CI: 0.966-1) in the discovery set. This study elucidated alterations and potential coregulatory influences of metabolites and proteins in the blood of IS patients.

Vegetable and Fruit Intake and LOX-Index in Japanese Municipal Workers.

Vegetable and fruit intake has been reported to be associated with decreased risk of cardiovascular disease. To date, however, no study has examined the association between vegetable and fruit intake and LOX-index, which reflects the progression of atherosclerosis and is a predictive biomarker of stroke and coronary heart disease. Here, we examined the cross-sectional association between vegetable and fruit intake and LOX-index in Japanese municipal workers. Participants were 338 workers (166 men and 172 women aged 19-71 y) with no history of serious disease who participated in a health and nutrition survey. Vegetable and fruit intake was assessed using a validated brief self-administered diet history questionnaire. LOX-index was calculated by multiplying serum concentrations of the soluble form of lectin-like oxidized LDL receptor-1 by those of LOX-1 ligands containing apolipoprotein B. Multiple regression analysis was used to estimate the geometric mean of LOX-index according to tertile of vegetable and/or fruit intake. Total vegetable and fruit intake was associated with a trend toward decreased LOX-index after adjustment for covariates (p for trend=0.067). In stratified analyses by sex, a significant inverse association between total vegetable and fruit intake and LOX-index was observed in women (p for trend=0.023), whereas such association was not observed in men (p for trend=0.70). None of the intakes of vegetables, fruit, green and yellow vegetables, or other vegetables was associated with LOX-index. Our results suggest that higher intake of total vegetables and fruit is associated with a lower LOX-index in Japanese women.

Matrix Metalloproteinases as Biomarkers for Ischemic Stroke: A Systematic Review

Background: Ischemic stroke, a leading cause of mortality and disability worldwide, occurs due to the disruption of blood flow to the brain, resulting in neuronal damage and death. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a crucial role in the pathophysiology of ischemic stroke by degrading the extracellular matrix and contributing to blood-brain barrier disruption, inflammation, and neuronal cell death. This systematic review aims to comprehensively evaluate the current evidence regarding the potential of MMPs as biomarkers for ischemic stroke diagnosis, prognosis, and therapeutic monitoring. Methods: A systematic search of electronic databases (PubMed, Embase, and Cochrane Library) was conducted to identify relevant studies published between 2018 and 2024. Studies investigating the association between MMPs and ischemic stroke in human subjects were included. Data extraction and quality assessment were performed independently by two reviewers. Results: The search yielded 2,182 articles, of which 8 studies met the inclusion criteria. The included studies evaluated various MMPs, including MMP-2, MMP-3, MMP-9, and MMP-12, in different biological samples (serum, plasma, cerebrospinal fluid, and brain tissue) from ischemic stroke patients. The majority of studies reported elevated levels of MMPs in ischemic stroke patients compared to healthy controls, with MMP-9 being the most extensively studied. Furthermore, several studies demonstrated a correlation between MMP levels and stroke severity, functional outcome, and the risk of hemorrhagic transformation. Conclusion: The findings of this systematic review suggest that MMPs, particularly MMP-9, hold promise as potential biomarkers for ischemic stroke. However, further research is needed to validate their clinical utility and to explore their potential as therapeutic targets.