• Patients with myocardial infarction have altered platelet miRNA profiles.• Activated platelets release miRNAs that can be taken up by endothelial cells and regulate ICAM-1 gene expression.Platelets play a crucial role in the pathogenesis of myocardial infarction (MI) by adhering to the site of a ruptured atherosclerotic plaque. The aim of this study was to screen for differences in the micro RNA (miRNA) content of platelets from patients with myocardial infarction and control patients, to investigate a possible release of miRNAs from activated platelets and to elucidate whether platelet-derived miRNAs could act as paracrine regulators of endothelial cell gene expression. Using RNA-seq, we found 9 differentially expressed miRNAs in patients compared with healthy controls, of which 8 were decreased in patients. Of these, miR-22, -185, -320b, and -423-5p increased in the supernatant of platelets after aggregation and were depleted in thrombi aspirated from MI patients, indicating the release of certain miRNAs from activated platelets. To confirm that endothelial cells could take up the released platelet miRNAs, transfer of both fluorescently labeled miRNA and exogenous celmiR-39 from activated platelets to endothelial cells was shown. Finally, a possible paracrine role of released platelet miR-320b on endothelial cell intercellular adhesion molecule-1 expression was shown. Thus, platelets from patients with MI exhibit loss of specific miRNAs, and activated platelets shed miRNAs that can regulate endothelial cell gene expression.
Cancer in the oral cavity is often preceded by precursor lesions. Nine oral mucosal disorders are known to have an increased risk of malignant transformation. The etiology varies from disorders caused by exogenous factors such as tobacco and autoimmune inflammation to idiopathic or inherited genetic aberrations. In this review, these potentially malignant disorders (PMDs) are described regarding clinical presentation and histopathological architecture. Special attention is paid to the underlying etiologies of PMDs and the potential pathways leading to cancer. The clinical perspective focuses on the importance of accurate and timely diagnosis.
Oral leukoplakia (OL) is a potentially malignant oral disorder. The Gold Standard treatment is to remove surgically the OL. Despite optimal surgery, the recurrence rates are estimated to be 30%. The reason for this is unknown. The aim of this study was to investigate the clinical factors that correlate with recurrence after surgical removal of OL. In a prospective study data were collected from 226 patients with OL. Forty-six patients were excluded due to incomplete records or concomitant presence of other oral mucosal diseases. Overall, 180 patients proceeded to analysis (94 women and 86 men; mean age, 62 years; age range, 28–92 years). Clinical data, such as gender, diagnosis (homogeneous/non-homogeneous leukoplakia), location, size, tobacco and alcohol use, verified histopathological diagnosis, and clinical photograph, were obtained. In patients who were eligible for surgery, the OL was surgically removed with a margin. To establish recurrence, a healthy mucosa between the surgery and recurrence had to be confirmed in the records or clinical photographs. Statistical analysis was performed with the level of significance set at P<0.05. Of the 180 patients diagnosed with OL, 57% (N = 103) underwent surgical removal in toto. Recurrence was observed in 43 OL. The cumulative incidence of recurrence of OL was 45% after 4 years and 49% after 5 years. Fifty-six percent (N = 23) of the non-homogeneous type recurred. Among snuff-users 73% (N = 8) cases of OL recurred. A non-homogeneous type of OL and the use of snuff were significantly associated with recurrence after surgical excision (P = 0.021 and P = 0.003, respectively). Recurrence was also significantly associated with cancer transformation (P<0.001). No significant differences were found between recurrence and any of the following: dysplasia, site of lesion, size, multiple vs. solitary OL, gender, age, use of alcohol or smoking. In conclusion, clinical factors that predict recurrence of OL are non-homogeneous type and use of snuff.
TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.
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