A b s t r a c tBackground: The biochemical confirmation of myocardial infarction is based on cardiac troponin (cTnI or cTnT) determination. Recent scientific results suggested that microRNAs (miRNAs) might become a new biomarker of tissue injury. Aim:To evaluate the release kinetics of circulating heart-specific miRNA-208a and also to test the hypothesis that miRNA-208a can serve as an accessible, diagnostically sensitive plasma biomarker of ST-elevation acute myocardial infarction (STEMI). Methods:Nineteen STEMI patients (four women and 15 men, aged 44-85 years), 12 patients with stable coronary artery disease (CAD), and eight patients with a negative observation of CAD as a control group were studied. Blood samples were collected on admission and at three, six, 12, 24, and 48 h afterwards; in the CAD and control group blood samples were taken only once. Plasma levels of miRNA-208a determined by real-time polymerase chain reaction and their relative fold changes were calculated. cTnI and creatinine kinase (CK)-MB mass were also measured in the patients' serum samples.Results: miRNA-208a was increased in STEMI patients at the time of admission and nearly undetectable in CAD patients and controls. The peak of miRNA-208a was observed at 3 h after reperfusion (p < 0.001). The traditional biomarkers (cTnI and CK-MBmass), which increase later in comparison to miRNA-208a reaching the maximum concentrations 6 h after reperfusion, were observed. Circulating miRNA-208a levels strongly correlated with cTnI and CK-MBmass released from the infarcted area. Conclusions:These results demonstrate that plasma miRNA-208a is an interesting and promising candidate for a new biomarker released early after onset of myocardial infarction.
The aim of the present study was to analyze the profiles of cardiac microRNAs (miRNAs/miRs) in healthy pregnant women and non-pregnant controls. A total of 61 healthy women >18 years of age with singleton pregnancies in the third trimester were compared with 19 non-pregnant controls. Specifically, expression of miRNAs associated with cardiac hypertrophy (miR-1, miR-17-5, miR-22, miR-34a, miR-124, miR-133a, miR-195, miR-199a-3p, miR-199b, miR-210, miR-222 and miR-1249) and miRNAs associated with cardiac hypertrophy and fibrosis (miR-15b, miR-21, miR-26a, miR-29-a, miR-29c, miR-30c, miR-101, miR-146a, miR-191, miR-208a-5p and miR-328) were analyzed and compared with echocardiographic examination results. Both groups had similar cardiac miRNA expression profiles, but differed in quantitative evaluation. Women in the third trimester of physiological pregnancy exhibited downregulation of certain profibrotic miRNAs (miR-21, miR-30c and miR-328), decreased expression of a hypertrophic and antimetabolic miRNAs (miR-146a), downregulation of an antifibrotic miRNA (miR-222), and downregulation of a hypertrophic miRNA (miR-195). In pregnant women, the indices of systolic function were associated with miR-195 expression, and an interplay between miR-17-5p and diastolic function was observed. While the profiles of cardiac miRNAs expressed in healthy pregnant women and healthy non-pregnant controls were similar, these two groups differed in terms of expression of specific miRNAs. In the third trimester of physiological pregnancy, a downregulation of miR-17-5p, miR-21, miR-30c, miR-146a, miR-195, miR-222 and miR-328 was observed. The differences in the association between echocardiographic indices with miRNAs in pregnant and non-pregnant women suggest that miRNAs regulate both the structure and function of the pregnant heart, influencing cardiac muscle thickness as well as systolic and diastolic function.
In the 3rd trimester of physiological pregnancy, there is a 244% increase in expression of miR-101a and a decrease by 73% in expression of miR-328. Both of these changes can protect against fibrosis during volume overload occurring in physiological pregnancy.
Background/Aim: Patients with metastasized melanoma have limited treatment options and poor diagnosis. Therefore, the development of treatments requires a new therapeutic approach, of which gene therapy using rAAV vectors can be proposed. The aim of the study was to examine the efficiency of the rAAV vector to transduce mouse melanoma cells both in vitro and in vivo. Materials and Methods: Different rAAV serotypes encoding GFP under the control of both chicken beta-actin and cytomegalovirus promoters were used in the experiments. Intranasal, intraperitoneal, intravenous and intratumoral pathways of administration of rAAV vectors were tested using quantitative-PCR and immunohistochemical staining. Results: The highest transduction efficiency in metastatic cells in vivo was observed 7 days after intranasal administration of a 10 10 gc/0.03 ml dose of rAAV/DJ-CAG. Conclusion: Melanoma gene therapy based on rAAV vectors is a possible treatment option. Melanoma is a tumor that derives from pigment cellsmelanocytes, which develop from the neural tissue of integuments. The most common starting point of melanoma is the skin, but it may also be formed within the mucous membranes of the gastrointestinal tract or in the eyeball. It is a cancer with a high potential for metastasis (1, 2). Despite the progress in anti-cancer treatment, the number of deaths due to metastatic melanoma is still increasing and from the beginning of 2019 circa 7,000 patients in the USA died of it (1). Its aggressiveness causes as much as 90% of deaths among all skin cancers (3). The median survival of patients with melanoma who have distant metastases is shorter than 1 year (4). In the initial stage, the disease is curable, but unfortunately in the advanced stage, when metastasis occurs, it is practically incurable (5). The treatment, which has so far been proposed for the advanced stage, does not provide the desired benefit and the survival of these patients remains unsatisfactory. For instance, the annual survival rate after treatment with targeted therapy for the dual BRAF/MEK mutation is only about 50-60% (4, 6). Therefore, one of the future therapeutic approaches in the treatment of metastatic melanoma can be gene therapy using rAAV vectors, especially with the use of hybrid serotypes, which can achieve high efficiency of gene delivery (7-9). AAV viruses are non-pathogenic, small (approx. 25 nm in diameter) and infect both dividing and non-dividing cells. A distinguishing trait of rAAV is also the occurrence of various serotypes, which are characterized by strong tropism to selected cell types, making them ideal candidates for gene therapy (10). rAAV viruses have become increasingly popular in clinical trials (11, 12). In recent years, two pharmaceutical products using rAAV vectors-Glybera (13) and Luxturna (14) have been registered. Recent studies conducted on hybrid/mosaic serotypes have shown a greater transduction efficiency and are more heterogeneous, both in cellular and tissue specificity (15). The new rAAV vectors are created by a num...
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