miR-19a-3p containing exosomes improve function of ischemic myocardium upon shock wave therapy

AIMS: As many current approaches for heart regeneration exert unfavorable side-effects, the induction of endogenous repair mechanisms in ischemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischemia. METHODS AND RESULTS: Mechanical stimulation of ischemic muscle via SWT caused extracellular vesicle (EV) release from endothelial cells both in vitro and in vivo. Characterization of EVs via electron microscopy, nanoparticle tracking analysis and flow cytometry revealed specific exosome morphology and size with presence of exosome markers CD 9, CD81 and CD63. Exosomes exhibited angiogenic properties activating protein kinase b (Akt) and extracellular-signal regulated kinase (ERK) resulting in enhanced endothelial tube formation and proliferation. A miRNA array and transcriptome analysis via next-generation sequencing were performed to specify exosome content. miR-19a-3p was identified as responsible cargo, antimir-19a-3p antagonized angiogenic exosome effects. Exosomes and target miRNA were injected intramyocardially in mice after left anterior descending artery (LAD) ligation. Exosomes resulted in improved vascularization, decreased myocardial fibrosis and increased left ventricular ejection fraction as shown by transthoracic echocardiography. CONCLUSIONS: The mechanical stimulus of SWT causes release of angiogenic exosomes. miR-19a-3p is the vesicular cargo responsible for the observed effects. Released exosomes induce angiogenesis, decrease myocardial fibrosis and improve left ventricular function after myocardial ischemia. Exosome release via SWT could develop an innovative approach for the regeneration of ischemic myocardium

ESC Joint Working Groups on Cardiovascular Surgery and the Cellular Biology of the Heart Position Paper: Perioperative myocardial injury and infarction in patients undergoing coronary artery bypass graft surgery

International audienc

Comparing early adolescents’ positive bystander responses to cyberbullying and traditional bullying: the impact of severity and gender

Young people are frequently exposed to bullying events in the offline and online domain. Witnesses to these incidents act as bystanders and play a pivotal role in reducing or encouraging bullying behaviour. The present study examined 868 (47.2% female) 11-13-year-old early adolescent pupils’ bystander responses across a series of hypothetical vignettes based on traditional and cyberbullying events. The vignettes experimentally controlled for severity across mild, moderate, and severe scenarios. The findings showed positive bystander responses (PBRs) were higher in cyberbullying than traditional bullying incidents. Bullying severity impacted on PBRs, in that PBRs increased across mild, moderate, and severe incidents, consistent across traditional and cyberbullying. Females exhibited more PBRs across both types of bullying. Findings are discussed in relation to practical applications within the school. Strategies to encourage PBRs to all forms of bullying should be at the forefront of bullying intervention methods

Infection of the single-celled diatom Stephanodiscus alpinus by the chytrid Zygorhizidium: Parasite distribution within host population, changes in host cell size, and host-parasite size relationship.

An epidemic caused by a Zygorhizidium species infecting the single-celled planktonic centric diatom Stephanodiscus alpinus was analyzed for parasite distribution within the host population, final parasite size relative to host cell size, and size changes of infected and uninfected S. alpinus cells. Infections in the lake occurred at random within the whole host population. There was no evidence for aggregated or even distribution of the parasite individuals, indicating that the infections occur independently of each other. In enclosures in which light was enhanced compared to the lake, there tended to be an even parasite distribution within the host population, irrespective of whether plant nutrients were added. This suggests that infected host cells were negatively selected by the parasite zoospores under these conditions. Final parasite sporangium size and host cell size were positively correlated. Thus, parasite fecundity was limited by host cell size. Infected S. alpinus cells tended to be larger than uninfected cells, and the mean size of host cells within the population decreased during the epidemic. This might be due to selective infection of larger host cells or to the peculiar mode of cell division in diatoms

Relative abundance, rate of increase, and fungal infections of freshwater phytoplankton.

Fungal infections of seven species of phytoplankton were examined in relation to the host species' exponential rate of net increase, and to their proportional contribution to the total phytoplankton biovolume. Infections were observed to increase at biovolume proportions of the host species of as low as 1%. In most algal species, infected cells were always found at higher proportions, with the exception of Stephanodiscus rotula and Fragilaria crotonensis. In these two species, high proportions of biovolume were reached without any evidence of infected cells. The increase in infected cells was usually associated with a growing host population, whereas peak and decreasing densities of infected cells were usually observed when host populations were declining. The results show that the fungal parasites can exist on their host population even if it comprises only a small fraction of the total phytoplankton biovolume, and that the parasites become evident while the host population is still increasing

Fungal infections of the phytoplankton: seasonality, minimal host density, and specificity in a mesotrophic lake.

Phytoplankton infections by fungal parasites in the upper, mixed layer of a mesotrophic northern temperate lake were analysed according to the following parameters: host and parasite species, host population density and prevalence of infection, resting spore formation by the parasite, and the lowest host density at which parasites appeared. The phytoplankton taxa recorded included the Cyanobacteria, Dinomastigota, Chrysophyceae, Bacillariophyceae, Chlorophyceae, Cryptophyceae and Haptophyceae, but infection was never found in the last two classes. The parasites belonged almost exclusively to the monocentric Chytridiomycetes. Fungal epidemics occurred at all times of the year. Parasites appeared at population densities as low as about 1 cell ml⁻¹ in some host species, with infection prevalence sometimes exceeding 80%. The proportion of the total phytoplankton biovolume infected by fungi was usually much <1%, but occasionally reached 10%. Parasitism proved to be highly species-specific, with one parasite species usually infecting only one host species. In the case of Zygorhizidium planktonicum, which infected both Asterionella formosa and Synedra acus, there is evidence that two species-specific formae speciales, each infecting only one of these two host species, are present in the lake