Background/Aims Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. Recently, exosomes from cardiomyocytes (CMs) have been found to facilitate cell proliferation and survival by transporting various bioactive molecules, including circRNA. However, the functions of exosomal circRNAs are not clear. The present research is aimed at determining whether circHIPK3 released from hypoxia-pretreated CMs is transferred into cardiac microvascular endothelial cells (CMVECs) by exosomes and becomes functionally active in the CMVECs under oxidative stress conditions. Methods Quantitative polymerase chain reactions were conducted to detect the expression pattern of circHIPK3 in CMVECs under oxidative stress. Annexin V-FITC/propidium iodide (PI) staining assays, TUNEL assays, ROS assays, and Western blot analysis were conducted to detect the role of exosomal circHIPK3 in CMVEC function in vitro. Luciferase activity assays and RNA immunoprecipitation studies were conducted in vitro to reveal the mechanism of circHIPK3-mediated CMVEC function. Results circHIPK3 expression was significantly upregulated in hypoxic exosomes (HPC-exos) compared with normoxic exosomes (Nor-exos). Moreover, HPC-exos induced stronger antioxidant effects than Nor-exos. The silencing or overexpression of circHIPK3 changed CMVEC survival under oxidative conditions in vitro. Furthermore, circHIPK3 silencing in HPC-exos abrogated the protective effects of HPC-exos in CMVECs, as shown by increased levels of apoptosis, ROS, MDA, and proapoptotic proteins. circHIPK3 acted as an endogenous miR-29a sponge to sequester and inhibit miR-29a activity, which led to increased IGF-1 expression. The ectopic expression of miR-29a mimicked the effect of circHIPK3 silencing in CMVECs in vitro. Conclusions circHIPK3 in HPC-exos plays a role in CMVECs under oxidative conditions through miR-29a-mediated IGF-1 expression, leading to a decrease in oxidative stress-induced CMVECs dysfunction. These data suggest that the exosomal circRNA in CMs is a potential target to control CMVECs dysfunction under oxidative conditions.
An efficient organization of the educational process within rapid acceleration of the society digitization is impossible without increasing its digital literacy, if the latter is really estimated and new models of digital learning didactics are devel-oped respectively. So, it is necessary to study an actual state of digital literacy, as well as to search for and introduce new learning models in the educational system based on the use of modern innovative technologies and digital learning methods. The objective of the research is to examine the level of the digital literacy of teachers, and also opportunities and promising trends within the digital didactics for the formation of competencies as the basis of a new model for the develop-ment of a new learning model in the context of the formation of the digital knowledge society. Two main methods have been used – elaboration of the ab-stract and logical model and a survey. In the research the data obtained as a result of the survey conducted in 2018 by NAFI Analytical Centre related to the meas-urement of the digital literacy level of teachers and lecturers in Russia were used. The number of respondents made up 634 lecturers (higher education) as well as 555 teachers (general education). The digital literacy formation model was devel-oped based on the didactic learning triangle taking into account the synthesis of three learning environments – real, virtual and neurocognitive. The analysis of the survey data demonstrated that in the aggregate of the compared indices for differ-ent social groups of the population, school teachers and lecturers of higher educa-tional institutions have reached the higher level of the digital literacy, which sig-nificantly exceeds the average Russian level. So, in Russia as a whole the index of the digital literacy of the adult population by a similar measurement method makes up 52% out of 100% possible ones, school teachers – 87%, lecturers of higher educational institutions – 88%. The use of research results in practice is possible with the improvement of training programs, the exchange of internation-al experience and further researches.
Nowadays, sustainable construction (SC) is considered as a measure to support a healthy economy. The SC concept ensures quality of life and helps minimize the negative impact on the environment, human health, and biodiversity. SC fits into the modern sustainable development (SD) concept due to the ability to improve the environment, energy efficiency, and care for future generations. Despite numerous studies dedicated to the SC concept and implementation, practical matters related to SC including the importance of macroeconomic environmental sustainability are still insufficiently explored. The objective of this research is to study the practical issues of SC in the example of developing countries. Moreover, this work is aimed at determining the importance of the sustainable macroeconomic environment in ensuring SC. With the help of correlation and regression analysis effected for the purposes of the study, the direct connection and strong correlation between the GDP growth in the country and the number of large sustainable infrastructure facilities constructed and put into operation in the Russian Federation and China (correlation coefficient comprised 0.9987) were revealed. Within the current study, the experience of developing countries in SC is also discussed. It has been outlined that for emerging countries, the development of the construction industry environment within the framework of SC is possible in a sustainable business environment. The competitive advantages for SC are considered in social, economic, and environmental systems. Moreover, the models of formation and ensuring competitive advantages of the SC enterprise are presented. This paper reveals that the stability of the macroeconomic environment is a key factor in construction industry growth within the SC for developing countries.
The low survival rate of cardiac stem cells (CSCs) in the infarcted myocardium hampers cell therapy for ischemic cardiomyopathy. MicroRNA-21 (miR-21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c-kit+ CSC remain unclear. Thus, we hypothesized that miR-21 reduces hydrogen peroxide- (H2O2-) induced apoptosis in c-kit+ CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR-21 mimics efficiently reduced H2O2-induced apoptosis in c-kit+ CSC, as evidenced by the downregulation of the proapoptosis proteins caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2. In addition, the gain of function of miR-21 in c-kit+ CSC downregulated the protein level of PTEN although its mRNA level changed slightly; in the meantime, miR-21 overexpression also increased phospho-Akt (p-Akt). The antiapoptotic effects of miR-21 were comparable with Phen (bpV), the selective inhibitor of PTEN, while miR-21 inhibitor or PI3K's inhibitor LY294002 efficiently attenuated the antiapoptotic effect of miR-21. Taken together, these results indicate that the anti-H2O2-induced apoptosis effect of miR-21 in c-kit+ CSC is contributed by PTEN/PI3K/Akt signaling. miR-21 could be a potential molecule to facilitate the c-kit+ CSC therapy in ischemic myocardium.
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