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

Animals of different phenotype differentially utilise dietary niche- the case of the Great Grey Shrike Lanius excubitor

We tested the morphological trait utility in Great Grey Shrike Lanius excubitor. The food composition was used as an indicator of phenotype performance advantage in utilising of particular dietary niche. Mounts and accompanying data (measurements and stomach contents) from the Slovak extensive collection, involving adult birds obtained from April to October, were selected for analysis (n = 48). Ordination methods (redundancy analysis) and Generalized Linear Model regression show that the composition of the bird's food was non-random in respect to body characteristics. Tarsus and wing lengths were the most important morphometric predictors and ex- plained 12.7% of overall variance in food data. Smaller birds foraged mainly on Carabidae. Individuals with longer wings and tails more frequently preyed on flying and plant-dwelling insects. We conclude that phenotypic characteristics of an animal at least partially determine its diet

Potential Health Risk to Humans Related to Accumulation of Brodifacoum and Bromadiolone in the Wheat Grown on Rodenticide Contaminated Soil

The aim of this study was to determine in a model experiment the potential residues of bromadiolone and brodifacoum in the wheat grown on soil treated with these rodenticides and to compare them with the respective acceptable daily intake (ADI) in order to obtain information lacking in the scientific literature. The study focused on the level of residues of chronic rodenticides Broder G, with the active ingredient brodifacoum, and DERATION G, with the active ingredient bromadiolone, in wheat (Triticum spp.). The preparations were used in the form of granular bait. In the wheat grown on the soil treated with 100 g.m−2 of the preparation BRODER G, the brodifacoum residues ranged from 0.012 to 0.0218 mg.kg−1, while the treatment of soil with 500 g.m−2 resulted in residues ranging between 0.0344 and 0.0436 mg.kg−1. When using the preparation DE-RATION G, bromadiolone residues ranged between 0.012 and 0.018 mg.kg−1 after the treatment of soil with 100 g.m−2 and between 0.030 and 0.0428 mg.kg−1 after the treatment with 500 g.m−2. We observed that the acceptable daily intake was exceeded significantly in all of the cases and the residual levels depended on the rodenticide dose. In the case of brodifacoum, the ADI was exceeded more than 700-fold at a dose of 100 g.m−2 and more than 1400-fold at a dose of 500 g.m−2 of soil. With bromadio-lone, the ADI was exceeded 150-fold at a dose of 100 g.m−2 and more than 350-fold at a dose of 500 g.m−2. This indicates the risk to consumers from such crops

Effect of ovariohysterectomy on canine postsurgical leukocyte function

The effect of surgery on phagocytic activity of blood leukocytes and mitogen-induced blastogenesis of lymphocytes was studied in fourteen dogs. Simple ovariohysterectomy with anaesthesia induced by ketamine and xylazine or by ketamine, xylazine and halothane caused a short nonsignificant depression of phagocytic activity that persisted for four hours after surgery. Ingestion capacity of leukocytes decreased significantly immediately after surgery. Mitogen-induced blastogenesis of lymphocytes was depressed significantly in the first 48 hours and despite partial recovery this parameter did not reach the value of the control groups until the end of observation (7 days). A more conspicuous decrease of blastogenic response of blood lymphocytes to mitogens was found after the use of ketamine and xylazine in a dose maintaining anaesthesia. Anaesthesia with ketamine and xylazine in the lower dose and maintained with halothane resulted in a later improvement of the blastogenic response of lymphocytes