Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.     

Treatment of human neuroblastoma cell line SH-SY5Y with HSP27 siRNA tagged-exosomes decreased differentiation rate into mature neurons

Heat shock proteins (HSPs) participate in the regulation of different cell activities in response to stimuli. By applying different strategies, the modulation of heat shock proteins is at the center of attention. Conventional delivery approaches are not fully encouraged due to cytotoxicity and immunogenicity issues. Exosomes are touted as bio-shuttles for delivery of distinct biomolecules inside the cells. Here, we aimed to HSP27 small interfering RNA (siRNA)-tagged exosomes for the inhibition of Hsp27 in human neuroblastoma cell line SH-SY5Y and explored differentiation into neuron-like cells. Exosomes were isolated, characterized by scanning electron microscope (SEM) and CD63 then enriched with siRNA against Hsp27. Neuroblastoma cells were incubated with exosomes carrying siRNA for 48 hr. Exosome uptake was monitored by immunofluorescence assay. The cell viability and proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine/5-bromo-2′-deoxyuridine incorporation assays. The ability of cells to form colonies was evaluated by clonogenic assay. The cell potential to express NeuN, a mature neuron factor, was studied by flow cytometry analysis. SEM showed the nano-sized particles and a high level of CD63 after enrichment. Immunofluorescence imaging revealed an appropriate transfection rate in cell exposed to Hsp27 siRNA tagged exosomes. The cell viability and proliferation were reduced compared to cells received nude exosomes ( p < 0.05). Clonogenic activity of cells was diminished by the inhibition of Hsp27. Flow cytometry analysis revealed that the inhibition of Hsp27 prohibited NeuN content, showing the maturation of SH-SY5Y cells to mature cells compared to control. These data confirmed that exosomes could be used as appropriate bio-shuttles for the inhibition of Hsp27-aborted cell differentiation toward mature neuron.     

The Effect of Enriched Milk with Selenium and Vitamin E on Growth Rate, Hematology, Some Blood Biochemical Factors, and Immunoglobulins of Newborn Goat Kids

Thirty male and female (n?=?15 for each one) Markhoz newborn goat kids (aged 7?±?3 days) were distributed in a randomized block design in a 2?×?2?+?1 factorial arrangement: two levels of sodium selenite as a source of selenium (0.2 or 0.3 ppm Se), two levels of α-tocopherol acetate as a source of vitamin E (150 or 200 IU Vit E), and one control treatment with six repetitions per treatment (each replicate included three male and three female kids). Animals were fed daily by Se-Vit E-enriched milk (Se-Vit E treatments) or non-enriched milk (control treatment). Growth rate, hematology, and serum biological parameters were measured. The levels of serum albumin (P?<?0.01), serum globulin (P?<?0.05), total serum protein levels (P?<?0.01), erythrocyte counts (RBC) (P?<?0.001), hemoglobin (P?<?0.001), hematocrit (P?<?0.001), leukocyte counts (WBC) (P?<?0.001), IgA (P?<?0.05), IgG (P?<?0.01), and IgM (P?<?0.01) significantly differed among treatments, while no significant differences were observed for calcium, lymphocyte, neutrophil average daily gain and body weight among treatments. Kids feeding by enriched milk with 0.3 ppm Se and 200 IU Vit E had significantly higher serum total protein, globulin, RBC, IgA, IgG, and IgM compared to control and those fed by enriched milk to 0.2 ppm Se and 200 IU Vit E had significantly higher WBC counts.     

(Co)variance components and genetic parameters for growth traits in Arabi sheep using different animal models

The objective of the present study was to estimate genetic parameters for body weight at different ages in Arabi sheep using data collected from 1999 to 2009. Investigated traits consisted of birth weight (N = 2776), weaning weight (N = 2002) and weight at six months of age (N = 1885). The data were analyzed using restricted maximum likelihood analysis, by fitting univariate and multivariate animal models. All three weight traits were significantly influenced by birth year, sex and birth type. Age of dam only significantly affected birth weight. Log-likelihood ratio tests were conducted to determine the most suitable model for each growth trait in univariate analyses. Direct and total heritability estimates for birth weight, weaning weight and weight at six months of age (based on the best model) were 0.42 and 0.16 (model 4), 0.38 and 0.13 (model 4) and 0.14 and 0.14 (model 1), respectively. Estimation of maternal heritability for birth weight and weaning weight was 0.22 and 0.18, respectively. Genetic and phenotypic correlations among these traits were positive. Phenotypic correlations among traits were low to moderate. Genetic correlations among traits were positive and higher than the corresponding phenotypic correlations. Weaning weight had a strong and significant correlation with weight at six months of age (0.99). We conclude that selection can be made in animals based on weaning weight instead of the present practice of selection based on weight at six months.     

Predator-driven phenotypic diversification in Gambusia affinis

Predation is heterogeneously distributed across space and time, and is presumed to represent a major source of evolutionary diversification. In fishes, fast-starts--sudden, high-energy swimming bursts--are often important in avoiding capture during a predator strike. Thus, in the presence of predators, we might expect evolution of morphological features that facilitate increased fast-start speed. We tested this hypothesis using populations of western mosquitofish (Gambusia affinis) that differed in level of predation by piscivorous fish. Body morphology of G. affinis males, females, and juveniles diverged in a consistent manner between predatory environments. Fish collected from predator populations exhibited a larger caudal region, smaller head, more elongate body, and a posterior, ventral position of the eye relative to fish from predator-free populations. Divergence in body shape largely matched a priori predictions based on biomechanical principles, and was evident across space (multiple populations) and time (multiple years). We measured maximum burst-swimming speed for male mosquitofish and found that individuals from predator populations produced faster bursts than fish from predator-free populations (about 20% faster). Biomechanical models of fish swimming and intrapopulation morphology-speed correlations suggested that body shape differences were largely responsible for enhanced locomotor performance in fish from predator populations. Morphological differences also persisted in offspring raised in a common laboratory environment, suggesting a heritable component to the observed morphological divergence. Taken together, these results strongly support the hypothesis that divergent selection between predator regimes has produced the observed phenotypic differences among populations of G. affinis. Based on biomechanical principles and recent findings in other species, it appears that the general ecomorphological model described in this paper will apply for many aquatic taxa, and provide insight into the role of predators in shaping the body form of prey organisms.