Levels of Small Extracellular Vesicles Containing hERG-1 and Hsp47 as Potential Biomarkers for Cardiovascular Diseases.

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.

COVID-19 en Chile: análisis de su impacto por olas y regiones

Background: The effects of COVID-19 in Chile changed over time and among regions. Aim: To identify patterns in the impact and evolution of COVID-19 for each wave generated between 2020 and 2022 at the 16 regions of the country. Material and Methods: Several indicators related to the pandemic, their evolution and their consequences for the health system and the health of the population were calculated. Results: There are differences in the evolution of the infection across the regions of the country, as well as heterogeneity between waves. Specifically, the second wave in Chile was identified as the one with the greatest impact, with a national death rate of 123.5 deaths per 100,000 inhabitants and 66.4% intensive care unit occupancy rate due to COVID-19. Performing a geographic analysis, it was possible to find systematic patterns, for example, between regions with higher immunization rates and lower rates of lethality, such as the cases of Ñuble and Atacama regions. Conclusions: These results emphasize the need to consider regional differences and the temporal context for the elaboration of strategies to the efficient management of a pandemic.

[The impact of the different waves of COVID-19 pandemic in Chile across regions]. / COVID-19 en Chile: análisis de su impacto por olas y regiones.

BACKGROUND: The effects of COVID-19 in Chile changed over time and among regions. AIM: To identify patterns in the impact and evolution of COVID-19 for each wave generated between 2020 and 2022 at the 16 regions of the country. MATERIAL AND METHODS: Several indicators related to the pandemic, their evolution and their consequences for the health system and the health of the population were calculated. RESULTS: There are differences in the evolution of the infection across the regions of the country, as well as heterogeneity between waves. Specifically, the second wave in Chile was identified as the one with the greatest impact, with a national death rate of 123.5 deaths per 100,000 inhabitants and 66.4% intensive care unit occupancy rate due to COVID-19. Performing a geographic analysis, it was possible to find systematic patterns, for example, between regions with higher immunization rates and lower rates of lethality, such as the cases of Ñuble and Atacama regions. CONCLUSIONS: These results emphasize the need to consider regional differences and the temporal context for the elaboration of strategies to the efficient management of a pandemic.

A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission.

Stress is a widespread problem in today's societies, having important consequences on brain function. Among the plethora of mechanisms involved in the stress response at the molecular level, the role of microRNAs (miRNAs) is beginning to be recognized. The control of gene expression by these noncoding RNAs makes them essential regulators of neuronal and synaptic physiology, and alterations in their levels have been associated with pathological conditions and mental disorders. In particular, the excitatory (i.e., glutamate-mediated) neurotransmission is importantly affected by stress. Here, we found that loss of miR-26a-5p (miR-26a henceforth) function in primary hippocampal neurons increased the frequency and amplitude of miniature excitatory currents, as well as the expression levels of the excitatory postsynaptic scaffolding protein PSD95. Incubation of primary hippocampal neurons with corticosterone downregulated miR-26a, an effect that mirrored our in vivo results, as miR-26a was downregulated in the hippocampus as well as in blood serum-derived small extracellular vesicles (sEVs) of rats exposed to two different stress paradigms by movement restriction (i.e., stress by restraint in cages or by complete immobilization in bags). Overall, these results suggest that miR-26a may be involved in the generalized stress response and that a stress-induced downregulation of miR-26a could have long-term effects on glutamate neurotransmission.