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Tavares V, Savva-Bordalo J, Rei M, Liz-Pimenta J, Assis J, Pereira D, Medeiros R. Heritable Genetic Variability in Ovarian Tumours: Exploring Venous Thromboembolism Susceptibility and Cancer Prognosis in a Hospital-Based Study. Gene 2025; 950:149378. [PMID: 40032058 DOI: 10.1016/j.gene.2025.149378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/14/2025] [Accepted: 02/27/2025] [Indexed: 03/05/2025]
Abstract
Venous thromboembolism (VTE) is a frequently encountered paraneoplastic syndrome in patients with ovarian cancer (OC), an inflamm-aging entity. VTE is known to exacerbate their already poor prognosis, which is partially attributed to the contribution of the haemostatic system to ovarian tumourigenesis. In the past decade, numerous single-nucleotide polymorphisms (SNPs) implicated in VTE pathways have been proposed to influence tumour susceptibility and progression. These SNPs represent potential tools to improve the prognosis accuracy of OC patients. Hence, this study explored the influence of 12 haemostasis-associated SNPs on the risk for VTE, risk of OC progression and related death among 98 OC patients. The findings revealed a 20.5 % incidence of VTE, which was associated with more rapid disease progression and shorter survival times (log-rank test, p < 0.05). PROCR rs10747514 (AA/AG vs. GG; odds ratio (OR) = 3.67, p = 0.037) and SERPINE1 rs2070682 (CC/CT vs. TT; OR = 9.28, p = 0.040) were predictors of OC-related VTE development. Regarding patients' prognosis regardless of venous thrombogenesis, RGS7 rs2502448, F3 rs1361600, FGG rs2066865, and SERPINE1 rs2070682 were the most relevant biomarkers in different patient groups. These genetic variants might constitute attractive prognostic indicators among OC patients, offering insights to refine disease management strategies. However, due to the small cohort size and the study's retrospective nature, external validation is necessary to assess the generalisation of the findings.
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Affiliation(s)
- Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/CI-IPOP @RISE(Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal
| | - Joana Savva-Bordalo
- Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Mariana Rei
- Department of Gynaecology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Joana Liz-Pimenta
- Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal; Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Joana Assis
- Clinical Research Unit, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto. CCC), 4200-072 Porto, Portugal
| | - Deolinda Pereira
- Department of Medical Oncology, Portuguese Institute of Oncology of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/CI-IPOP @RISE(Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; Faculty of Medicine, University of Porto (FMUP), 4200-072 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal; Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal.
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Jiang W, Jiang L, Zhao X, Liu Y, Sun H, Zhou X, Liu Y, Huang S. Bioinformatics Analysis Reveals HIST1H2BH as a Novel Diagnostic Biomarker for Atrial Fibrillation-Related Cardiogenic Thromboembolic Stroke. Mol Biotechnol 2025; 67:2111-2126. [PMID: 38825608 DOI: 10.1007/s12033-024-01187-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 04/29/2024] [Indexed: 06/04/2024]
Abstract
Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.
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Affiliation(s)
- Wenbing Jiang
- Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, No.75 Jinxiu Road, Lucheng District, Wenzhou, 325000, Zhejiang Province, People's Republic of China.
| | - Lelin Jiang
- Second Clinical College of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China
| | - Xiaoli Zhao
- Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China
| | - Yiying Liu
- Postgraduate Training Base Allianceof Wenzhou Medical University (Wenzhou Central Hosptial), Wenzhou, Zhejiang, 325000, People's Republic of China
| | - Huanghui Sun
- The Dingli Clinical College of Wenzhou Medical University, Heart Function Examination Room, Wenzhou, Zhejiang, 325000, People's Republic of China
| | - Xinlang Zhou
- Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, No.75 Jinxiu Road, Lucheng District, Wenzhou, 325000, Zhejiang Province, People's Republic of China
| | - Yin Liu
- Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, No.75 Jinxiu Road, Lucheng District, Wenzhou, 325000, Zhejiang Province, People's Republic of China
| | - Shu'se Huang
- Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, No.75 Jinxiu Road, Lucheng District, Wenzhou, 325000, Zhejiang Province, People's Republic of China
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Jin M, Wang N, Li X, Zhang H, Zhou J, Cong M, Niu J, Lin C, Hu Y, Wu N, Liu J, Zhang K, Qiu C. Relationship between MTHFR C677T, homocysteine, and ischemic stroke in a large sample of the Han Chinese population. Medicine (Baltimore) 2022; 101:e30562. [PMID: 36197177 PMCID: PMC9509028 DOI: 10.1097/md.0000000000030562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Ischemic stroke, one of the prevalent causes of death and disability worldwide, is linked to environmental and genetic factors, including polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism. The present study aimed to explore the relationship between the MTHFR C677T variant, plasma homocysteine, and risk of developing large-artery atherosclerotic ischemic stroke (LAAIS) among Han Chinese. A population-based case-control study, which included 1810 patients with LAAIS and 1765 unrelated control subjects, was conducted. Compared to the controls, LAAIS patients had a significantly higher prevalence of hypertension, diabetes mellitus, smoking, and alcohol consumption (P < .001), as well as significantly higher mean fasting blood glucose, triglyceride, total cholesterol, and plasma homocysteine levels (P < .001). The TT homozygous genotype correlated with increased risk of developing LAAIS, as indicated by a significantly higher odds ratio (OR) compared to the CT and CC genotypes, in both additive (OR = 3.215, P = .01) and recessive models (OR = 3.265, P = .01). The plasma homocysteine level was genotype-dependent according to the following trend: TT > CT > CC. In conclusion, our data demonstrate that, in spite of its low prevalence in both patients and controls (1.5% vs 0.8%), the MTHFR C677T variant could, at least in part, affect homocysteine levels and this, either alone or in combination with other factors, increases the risk of LAAIS.
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Affiliation(s)
- Ming Jin
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Ningning Wang
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Xueyan Li
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Hao Zhang
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Jexin Zhou
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Mingyu Cong
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Jun Niu
- Mohe City Hospital, Mohe, Heilongjiang Province, People’s Republic of China
| | - Chongyang Lin
- Mohe City Hospital, Mohe, Heilongjiang Province, People’s Republic of China
| | - Ying Hu
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Nan Wu
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Jicheng Liu
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
| | - Keyong Zhang
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
- *Correspondence: Keyong Zhang, Institute of Medical Sciences, Qiqihar Medical University, 333 Bukui North Street, Qiqihar, Heilongjiang Province, 161006, People’s Republic of China (e-mail: )
| | - Changchun Qiu
- Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang Province, People’s Republic of China
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, People’s Republic of China
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Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke. Int J Mol Sci 2022; 23:ijms23094530. [PMID: 35562921 PMCID: PMC9102701 DOI: 10.3390/ijms23094530] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/04/2022] [Accepted: 04/14/2022] [Indexed: 02/06/2023] Open
Abstract
Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.
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Labib MW, Saadeldin A, El-Farrash R, Hassan MA, ElSakhawy Y, Abou Elwafa MAMA. Platelet glycoprotein VI genetic polymorphism T13254C in neonatal sepsis. THE EGYPTIAN JOURNAL OF HAEMATOLOGY 2022. [DOI: 10.4103/ejh.ejh_74_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Janicki PK, Eyileten C, Ruiz-Velasco V, Pordzik J, Czlonkowska A, Kurkowska-Jastrzebska I, Sugino S, Imamura Kawasawa Y, Mirowska-Guzel D, Postula M. Increased burden of rare deleterious variants of the KCNQ1 gene in patients with large‑vessel ischemic stroke. Mol Med Rep 2019; 19:3263-3272. [PMID: 30816480 DOI: 10.3892/mmr.2019.9987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 01/30/2019] [Indexed: 11/06/2022] Open
Abstract
The impact of rare and damaging variants in genes associated with platelet function in large‑vessel ischemic stroke (LVIS) remains unknown. The aim of this study was to investigate the contribution of some of these variants to the genetic susceptibility to LVIS in Polish patients using a deep re‑sequencing of 54 selected genes, coding for proteins associated with altered platelet function. Targeted pooled re‑sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of LVIS) and 500 age‑, smoking status‑, and sex‑matched controls (no history of any type of stroke), and from the same population as patients with LVIS. After quality control and prioritization based on allele frequency and damaging probability, individual genotyping of all deleterious rare variants was performed in patients from the original cohort, and stratified to concomitant cardiac conditions differing between the study and stroke groups. We demonstrated a statistically significant increase in the number of rare and potentially damaging variants in some of the investigated genes in the LVIS pool (an increase in the genomic variants burden). Furthermore, we identified an association between LVIS and 6 rare functional and damaging variants in the Kv7.1 potassium channel gene (KCNQ1). The predicted functional properties (partial loss‑of function) for the three most damaging variants in KCNQ1 coding locus were further confirmed in vitro by analyzing the membrane potential changes in cell lines co‑transfected heterogeneously with human muscarinic type 1 receptor and wild‑type or mutated KCNQ1 cDNA constructs using fluorescence imaging plate reader. The study demonstrated an increased rare variants burden for 54 genes associated with platelet function, and identified a putative role for rare damaging variants in the KCNQ1 gene on LVIS susceptibility in the Polish population.
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Affiliation(s)
- Piotr K Janicki
- Perioperative Genomics Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA
| | - Ceren Eyileten
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw 02‑097, Poland
| | - Victor Ruiz-Velasco
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA
| | - Justyna Pordzik
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw 02‑097, Poland
| | - Anna Czlonkowska
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw 02‑097, Poland
| | | | - Shigekazu Sugino
- Perioperative Genomics Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA
| | | | - Dagmara Mirowska-Guzel
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw 02‑097, Poland
| | - Marek Postula
- Perioperative Genomics Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA
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Eyileten C, Mirowska-Guzel D, Milanowski L, Zaremba M, Rosiak M, Cudna A, Kaplon-Cieslicka A, Opolski G, Filipiak KJ, Malek L, Postula M. Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus. Can J Diabetes 2019; 43:19-26. [DOI: 10.1016/j.jcjd.2018.01.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 01/31/2018] [Indexed: 01/23/2023]
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Sokol J, Skerenova M, Biringer K, Simurda T, Kubisz P, Stasko J. Glycoprotein VI Gene Variants Affect Pregnancy Loss in Patients With Platelet Hyperaggregability. Clin Appl Thromb Hemost 2018; 24:202S-208S. [PMID: 30278775 PMCID: PMC6714835 DOI: 10.1177/1076029618802358] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The aim of our study was to evaluate GP6 gene in patients with sticky platelet
syndrome (SPS) and fetal loss. Platelet aggregability was tested with
platelet-rich plasma using PACKS-4 aggregometer (Helena Laboratories).
High-resolution melting analysis on LightCycler 480 II (Roche Diagnostics) was
used for single-nucleotide polymorphism (SNP) genotyping. We examined 64
patients with SPS and 54 control participants. We found significantly higher
occurrence of 5 SNPs in patients with SPS versus controls (rs1671152, rs1654433,
rs1613662, rs1654416, and rs2304167). Moreover, the haplotype analysis showed a
significantly higher occurrence of 7 haplotypes in patients with SPS compared to
controls (acgg and aagg in GP6_5reg haplotype; ccgt in GP6_3reg haplotype; gg
and ta in GP6_REG haplotype; SKTH and PEAN in GP6_PEAN haplotype). Our results,
especially higher occurrence of 4 nonsynonymous variants within the coding
region, support the idea that GP6 polymorphisms are associated with the platelet
hyperaggregability accompanied by fetal loss.
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Affiliation(s)
- Juraj Sokol
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Maria Skerenova
- Department of Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Kamil Biringer
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Tomas Simurda
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Peter Kubisz
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Jan Stasko
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
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Pordzik J, Pisarz K, De Rosa S, Jones AD, Eyileten C, Indolfi C, Malek L, Postula M. The Potential Role of Platelet-Related microRNAs in the Development of Cardiovascular Events in High-Risk Populations, Including Diabetic Patients: A Review. Front Endocrinol (Lausanne) 2018; 9:74. [PMID: 29615970 PMCID: PMC5869202 DOI: 10.3389/fendo.2018.00074] [Citation(s) in RCA: 89] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 02/19/2018] [Indexed: 12/13/2022] Open
Abstract
Platelet activation plays a pivotal role in the development and progression of atherosclerosis, which often leads to potentially fatal ischemic events at later stages of the disease. Platelets and platelet microvesicles (PMVs) contain large amounts of microRNA (miRNA), which contributes largely to the pool of circulating miRNAs. Hence, they represent a promising option for the development of innovative diagnostic biomarkers, that can be specific for the underlying etiology. Circulating miRNAs can be responsible for intracellular communication and may have a biological effect on target cells. As miRNAs associated to both cardiovascular diseases (CVD) and diabetes mellitus can be measured by means of a wide array of techniques, they can be exploited as an innovative class of smart disease biomarkers. In this manuscript, we provide an outline of miRNAs associated with platelet function and reactivity (miR-223, miR-126, miR-197, miR-191, miR-21, miR-150, miR-155, miR-140, miR-96, miR-98) that should be evaluated as novel biomarkers to improve diagnostics and treatment of CVD.
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Affiliation(s)
- Justyna Pordzik
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Pisarz
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
| | - Salvatore De Rosa
- Division of Cardiology, Department of Medical and Surgical Sciences, “Magna Graecia” University, Catanzaro, Italy
| | - Axel Dyve Jones
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
| | - Ceren Eyileten
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
| | - Ciro Indolfi
- Division of Cardiology, Department of Medical and Surgical Sciences, “Magna Graecia” University, Catanzaro, Italy
- URT-CNR, Department of Medicine, Consiglio Nazionale delle Ricerche of IFC, Catanzaro, Italy
| | - Lukasz Malek
- Faculty of Rehabilitation, University of Physical Education, Warsaw, Poland
| | - Marek Postula
- Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
- *Correspondence: Marek Postula,
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Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1-P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients. Int J Mol Sci 2017; 18:ijms18122678. [PMID: 29232918 PMCID: PMC5751280 DOI: 10.3390/ijms18122678] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 12/05/2017] [Accepted: 12/07/2017] [Indexed: 01/13/2023] Open
Abstract
The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population.
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González-Del Castillo J, Candel FJ, Manzano-Lorenzo R, Arias L, García-Lamberechts EJ, Martín-Sánchez FJ. Predictive score of haematological toxicity in patients treated with linezolid. Eur J Clin Microbiol Infect Dis 2017; 36:1511-1517. [PMID: 28343274 DOI: 10.1007/s10096-017-2960-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 03/03/2017] [Indexed: 10/19/2022]
Abstract
OBJECTIVE The aims of our study were to determine the factors associated with developing haematological toxicity (HT) in patients taking linezolid (LZD), to develop a predictive model of HT in these patients, and to evaluate factors associated with 30-day mortality. METHODS This was an observational retrospective cohort study of patients treated for at least 5 days with LDZ in 2015. Demographic, clinical and analytical data were collected. Development of HT was defined as a 25% platelet count decrease between the basal count and the 1-week lab test. RESULTS Five hundred forty-nine patients were finally included, mean age was 73.3 (SD 15.4) years, and 303 (55.2%) were men. One hundred seventy-five (30.1%) patients achieved HT criteria during treatment with LZD and 41 (7.5%) died. The final model included the presence of cerebrovascular disease (2 points), moderate or severe liver disease (2 points), renal failure (2 points) and basal platelet count less than 90,000/mm3 (8 points). This new model showed an AUC of 0.711 (IC 95% 0.664-0.757; p < 0.001) to predict the development of HT. The probability of HT based on this classification was 6.2, 29.9 and 76.5% for low (0-4 points), intermediate (5-10 points) and high risk (>10 points), respectively. The independent variables associated with 30-day mortality were metastatic solid tumor, lymphoma, age >75 years and HT. CONCLUSION This score could help in the identification of patients with high risk for HT and assess the use of an antibiotic other than LZD, an important issue considering its relation with 30-day mortality observed in our study.
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Affiliation(s)
- J González-Del Castillo
- Emergency Department, Hospital Universitario Clínico San Carlos, Calle Profesor Martín-Lagos s/n, 28040, Madrid, Spain. .,Health Research Institute, Hospital Universitario Clínico San Carlos, Madrid, Spain.
| | - F J Candel
- Health Research Institute, Hospital Universitario Clínico San Carlos, Madrid, Spain.,Department of Clinical Microbiology, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - R Manzano-Lorenzo
- Pharmacy Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - L Arias
- Pharmacy Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - E J García-Lamberechts
- Emergency Department, Hospital Universitario Clínico San Carlos, Calle Profesor Martín-Lagos s/n, 28040, Madrid, Spain.,Health Research Institute, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - F J Martín-Sánchez
- Emergency Department, Hospital Universitario Clínico San Carlos, Calle Profesor Martín-Lagos s/n, 28040, Madrid, Spain.,Health Research Institute, Hospital Universitario Clínico San Carlos, Madrid, Spain
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Postula M, Janicki PK, Milanowski L, Pordzik J, Eyileten C, Karlinski M, Wylezol P, Solarska M, Czlonkowka A, Kurkowska-Jastrzebka I, Sugino S, Imamura Y, Mirowska-Guzel D. Association of frequent genetic variants in platelet activation pathway genes with large-vessel ischemic stroke in Polish population. Platelets 2016; 28:66-73. [DOI: 10.1080/09537104.2016.1203404] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Marek Postula
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
- Perioperative Genomics Laboratory, Penn State University, College of Medicine, Hershey, PA, USA
| | - Piotr K. Janicki
- Perioperative Genomics Laboratory, Penn State University, College of Medicine, Hershey, PA, USA
| | - Lukasz Milanowski
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Justyna Pordzik
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Ceren Eyileten
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Michal Karlinski
- 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Pawel Wylezol
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Marta Solarska
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Anna Czlonkowka
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
- 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | | | - Shigekazu Sugino
- Perioperative Genomics Laboratory, Penn State University, College of Medicine, Hershey, PA, USA
| | - Yuka Imamura
- Genome Sciences Facility, Penn State University, College of Medicine, Hershey, PA, USA
| | - Dagmara Mirowska-Guzel
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
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