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.

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 cancer stem cells from human colon adenocarcinoma cell line HT-29 with resveratrol and sulindac induced mesenchymal-endothelial transition rate.

In the current experiment, the combined regime of resveratrol and a Wnt-3a inhibitor, sulindac, were examined on the angiogenic potential of cancer stem cells from human colon adenocarcinoma cell line HT-29 during 7 days. Cancer stem cells were enriched via a magnetic-activated cell sorter technique and cultured in endothelial induction medium containing sulindac and resveratrol. Expression of endothelial markers such as the von Willebrand factor (vWF) and vascular endothelial cadherin (VE-cadherin) and genes participating in mesenchymal-to-epithelial transition was studied by real-time PCR assay. Protein levels of Wnt-3a and angiogenic factor YKL-40 were examined by western blotting. ELISA was used to determine the level of N-acetylgalactosaminyltransferase 11 (GALNT11) during mesenchymal-endothelial transition. Autophagy status was monitored by PCR array under treatment with the resveratrol plus sulindac. Results showed that resveratrol and sulindac had the potential to decrease the cell survival of HT-29 cancer cells and the clonogenic capacity of cancer stem cells compared with the control (p < 0.05). The expression of VE-cadherin and vWF was induced in cancer stem cells incubated with endothelial differentiation medium enriched with resveratrol (p < 0.05). Interestingly, the Wnt-3a level was increased in the presence of resveratrol and sulindac (p < 0.05). YKL-40 was reduced after cell exposure to sulindac and resveratrol. The intracellular content of resistance factor GALNT11 was diminished after treatment with resveratrol (p < 0.05). Resveratrol had the potential to induce the transcription of autophagy signaling genes in cancer stem cells during endothelial differentiation (p < 0.05). These data show that resveratrol could increase cancer stem cell trans-differentiation toward endothelial lineage while decrease cell resistance by modulation of autophagy signaling and GALNT11 synthesis.

Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.

Alzheimer's disease is associated with biochemical and histopathological changes characterized by molecular abnormalities. Due to the lack of effective treatments for Alzheimer's disease, many attempts have been made to find potential therapies to reduce or even return neuronal loss after disease initiation. Alzheimer's disease is also touted as type III diabetes, showing an association with insulin signaling. The large distribution of the insulin receptor on the cell surface and its regulatory role in the central nervous system suggests that the pathogenesis of Alzheimer's disease could be ascribed to insulin signaling. The interference of opioids, such as morphine with insulin signaling pathways, is thought to occur via direct crosstalk between the signaling pathways of the insulin receptor and the mu-opioid receptor. In this review article, we discuss the possible crosstalk between the mu-opioid receptor and insulin signaling pathways. The association of these two signaling pathways with Alzheimer's disease is also debated.

Correction to: Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.

The original version of this article unfortunately contained mistake in the Author Group section. Reza Rahbarghazi's family name was inadvertently spelled as "Rahbarghzi".