ABSTRACT
Introduction: SARS-CoV-2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable state seen in patients with COVID-19. Methodology: Using the original bioinformatic workflow and network medicine approaches we reanalyzed four coronavirus-related expression datasets and performed co-expression analysis focused on thrombosis and ACE2 related genes. We identified microRNAs (miRNAs) which play role in ACE2-related thrombosis in coronavirus infection and further, we validated the expressions of those miRNAs in 79 hospitalized COVID-19 patients and 32 healthy volunteers by PCR and monitored miRNAs patterns during the acute phase of COVID-19, as well as the prognostic potential of these miRNAs as biomarkers. Result(s): We identified EGFR, HSP90AA1, APP, TP53, PTEN, UBC, FN1, ELAVL1 and CALM1 as regulatory genes which could play a pivotal role in COVID-19 related thrombosis. We also found miR-16-5p, miR-27a-3p, Let- 7b-5p and miR-155-5p as regulators in coagulation and thrombosis process. We observed in separate cohort of COVID-19 patients and healthy controls that (i) expression of miR-16-5p, miR-27a-3p and miR-155-5p increased during observation, compared to the baseline measurement;(ii) a low baseline miR-16-5p expression presents predictive utility in assessment of the hospital length of stay or death in follow-up as a composite endpoint (AUC: 0.810, 95% CI, 0.71-0.91, p<0.0001);(iii) low baseline expression of miR-16-5p and diabetes mellitus are independent predictors of increased length of stay or death according to a multivariate analysis (OR: 9.417;95% CI, 2.647-33.506;p=0.0005 and OR: 6.257;95% CI, 1.049- 37.316;p=0.044, respectively). Conclusion(s): This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual. (Figure Presented) .
ABSTRACT
Background: Various miRNAs, as well as their target genes are involved in the complex pathophysiology of inflammation, immune response, coagulation and CVDs. Thus, they may be useful for diagnosis, prognosis and as a potential therapeutic strategy in multiple pathologies. Aim(s): According to our previously published bioinformatics analysis, we aimed to analyze the diagnostic and predictive utility of miRNAs regulating ACE2 network (miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-200b-3p, hsa-miR-124-3p) in patients with COVID-19. Result(s): The expression levels of miR-26b-5p in COVID-19 patients were found lower at the baseline, 7 and 21-days after admission. compared to the healthy controls (p<0.0001 for all time points). Similarly, miR-10b-5p expression levels were lower at the baseline and 21-days post admission in COVID-19 patients when compared to the healthy individuals (p=0.001 in both time points). Moreover, expression levels of this miRNA were higher 7- days post-admission when compared to the baseline (p=0.003). According to the ROC curve analysis, low miR-200b-3p expression presents predictive utility in assessment of the hospital length of stay and/or death (AUC: 0.730, p=0.002). According to the multivariable logistic regression model, low delta miR-200p expression, together with diabetes mellitus (DM), are independent predictors of increased hospital length of stay and/or death (OR: 5.775;95% CI, 1.572-21.214;p=0.008 and OR: 4.888;95% CI, 1.001-23.858;p=0.050, respectively). Conclusion(s): This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual. (Figure Presented) .
ABSTRACT
Measures to increase debt sustainability and related creditworthiness play an important role in sovereign fiscal policy. The establishing of fiscal rules delimits fiscal policy through specific limits for particular budget aggregates. Fiscal rules in Poland were analyzed against measures applied in European Union countries, with emphasis on changes due to COVID-19. Also differences in fiscal rules at the regional and local level in the United States, China, and Poland are described. Conclusions from the research lead to the identification of a relationship between the restrictiveness of the rules and possibilities to maintain budget balance and prevent excessive indebtedness. Important conclusions may be also drawn from different reactions for crisis in the fiscal rules area – from relaxing the rules to wide use of special fund or financial vehicles – which were crucial states reply to fiscal burdens. © 2023 Lex localis.
ABSTRACT
Background: SARS-CoV- 2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable state seen in patients with COVID-19. Aim(s): According to our previously published bioinformatics analysis, we aimed to analyze the diagnostic and predictive utility of miRNAs regulating ACE2 network (miR-26b- 5p, miR-10b- 5p, miR-302c- 5p, hsa-miR- 200b- 3p, hsa-miR- 124- 3p) in patients with COVID-19 Methods: We determined the expressions of ACE2-related- miRNAs in 79 hospitalized COVID-19 patients and 32 healthy volunteers by PCR and monitored miRNAs patterns during the acute phase of COVID-19, as well as the prognostic potential of these miRNAs as biomarkers. Result(s): The expression levels of miR-26b- 5p in COVID-19 patients were found lower at the baseline, 7 and 21-days after admission. compared to the healthy controls (p < 0.0001 for all time points). Similarly, miR-10b- 5p expression levels were lower at the baseline and 21-days post admission in COVID-19 patients when compared to the healthy individuals (p = 0.001 in both time points). Moreover, expression levels of this miRNA were higher 7-days post-admission when compared to the baseline (p = 0.003). According to the ROC curve analysis, low miR-200b- 3p expression presents predictive utility in assessment of the hospital length of stay and/or death (AUC:0.730, p = 0.002). According to the multivariable logistic regression model, low delta miR-200p expression, together with diabetes mellitus (DM), are independent predictors of increased hospital length of stay and/or death (OR: 5.775;95% CI, 1.572-21.214;p = 0.008 and OR: 4.888;95% CI, 1.001-23.858;p = 0.050, respectively). Conclusion(s): This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual. (Figure Presented).
ABSTRACT
Background: SARS-CoV- 2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable state seen in patients with COVID-19. Aim(s): We aimed identify microRNAs (miRNAs) play role in ACE2-related thrombosis in coronavirus infection and validated the expressions of those miRNAs in 79 hospitalized COVID-19 patients and 32 healthy volunteers and monitored miRNAs patterns during the acute phase of COVID-19, as well as the prognostic potential biomarker. Method(s): Using the original bioinformatic workflow and network medicine approaches we reanalyzed four coronavirus-related expression datasets and performed co-expression analysis focused on thrombosis and ACE2 related genes. Blood RNA;quality RNA was assessed: Fluorometric assay;RT-PCR for miRNAs expression measurement. Result(s): We identified EGFR, HSP90AA1, APP, TP53, PTEN, UBC, FN1, ELAVL1 and CALM1 as regulatory genes which could play a pivotal role in COVID-19 related thrombosis. We also found miR-16- 5p, miR-27a- 3p, Let-7b- 5p and miR-155- 5p as regulators in coagulation and thrombosis process. We observed in separate cohort of COVID-19 patients and healthy controls that (i) expression of miR-16- 5p, miR-27a- 3p and miR-155- 5p increased during observation, compared to the baseline measurement;(ii) a low baseline miR-16- 5p expression presents predictive utility in assessment of the hospital length of stay or death in follow-up as a composite endpoint (AUC:0.810, 95% CI, 0.71-0.91, p < 0.0001);(iii) low baseline expression of miR-16- 5p and T2DM are independent predictors of increased length of stay or death according to a multivariate analysis (OR: 9.417;95% CI, 2.647-33.506;p = 0.0005 and OR: 6.257;95% CI, 1.049-37.316;p = 0.044). Conclusion(s): This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual. (Figure Presented).