Exosomes for angiogenesis induction in ischemic disorders

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to “cure” ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100–150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed.     

Effect of In Ovo Feeding of the Vitamin B12 on Hatchability,Performance and Blood Constitutes in Broiler Chicken

International Journal of Peptide Research and Therapeutics - The aim of the current study was to determine effect of in ovo feeding of vitamin B12 on hatchability, growth performance and blood...     

Toxoplasma gondii profilin and tachyzoites RH strain may manipulate autophagy via downregulating Atg5 and Atg12 and upregulating Atg7

Molecular Biology Reports - Autophagy process is an important defense mechanism against intracellular infection. This process plays a critical role in limiting the development of Toxoplasma gondii....     

CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel

Molecular Biology Reports - One of the major barriers in cancer therapy is the resistance to conventional therapies and cancer stem cells (CSCs) are among the main causes of this problem. CD133 as...     

Effects of Zinc Supplement on Plasma Homocysteine Level in End-Stage Renal Disease Patients: a Double-Blind Randomized Clinical Trial

Increased homocysteine (hCys) level is an independent risk factor for cardiovascular complications in end-stage renal disease (ESRD) patients. The aim of this study was to evaluate effect of zinc (Zn) supplement on serum hCys level in ESRD patients. One hundred ESRD patients with Zn deficiency were enrolled in this double-blind randomized clinical trial. They were randomly subdivided into two groups and supplemented with Zn (Zn group) or placebo (control group) for 6 weeks. Fasting plasma hCys and Zn levels were measured before and at 43rd days after the start of the study. Serum Zn levels increased significantly (p?<?0.0001), in Zn-treated group in comparison to placebo-treated group. In the Zn-treated group, serum hCys levels reduced significantly (p?<?0.0001), compared to placebo group (p?>?0.05). There was a significant (p?<?0.0001) reduction of mean percentage of hCys in Zn-treated group compared to the placebo group. Our study showed that Zn supplementation decreases serum hCys levels in ESRD patients with Zn deficiency.     

A sensitive fluorescent nanosensor for chloramphenicol based on molecularly imprinted polymer‐capped CdTe quantum dots

A novel fluorescent nanosensor using molecularly imprinted silica nanospheres embedded CdTe quantum dots (CdTe@SiO₂@MIP) was developed for detection and quantification of chloramphenicol (CAP). The imprinted sensor was prepared by synthesis of molecularly imprinting polymer (MIP) on the hydrophilic CdTe quantum dots via reverse microemulsion method using small amounts of solvents. The resulting CdTe@SiO₂@MIP nanoparticles were characterized by fluorescence, UV–vis absorption and FT‐IR spectroscopy and transmission electron microscopy. They preserved 48% of fluorescence quantum yield of the parent quantum dots. CAP remarkably quenched the fluorescence of prepared CdTe@SiO₂@MIP, probably via electron transfer mechanism. Under the optimal conditions, the relative fluorescence intensity of CdTe@SiO₂@MIP decreased with increasing CAP by a Stern–Volmer type equation in the concentration range of 40–500 µg L^–1. The corresponding detection limit was 5.0 µg L^–1. The intra‐day and inter‐day values for the precision of the proposed method were all <4%. The developed sensor had a good selectivity and was applied to determine CAP in spiked human and bovine serum and milk samples with satisfactory results. Copyright © 2015 John Wiley & Sons, Ltd.     

W323S variant of Xiap-Bir3 binds to SMAC but not caspase-9

The ability of the wild-type XIAP BIR3 domain as well as its Trp323Ser variant in inhibition of human caspase-9, binding to AVPFVASLPN (SMAC-peptide), SMAC protein, and mature caspase-9 was investigated. In order to investigate the role of W323 on these interactions, this residue was mutated to Serine. Circular dichroism as well as thermal denaturation studies showed that W323S mutation did not hamper proper folding of the protein. The dissociation constants for the interaction of the wild type BIR3 as well as its mutant to Smac-type peptide were found to be 1.8 and 27 muM, respectively. The inhibition of and binding to caspase-9 by wild-type BIR3 and its mutant were also compared. While the wild-type protein potently inhibited the enzyme, the mutant failed to do so. The lack of caspase-9 inhibition was due to absence of interaction of the mutant BIR3 with mature caspase-9. These results indicate that Trp323 of BIR3 plays a pivotal role both in maintaining necessary conformation for caspase-9 interaction and to a lesser extent, recognition of Smac-type peptide. Moreover, decreased stability of the mutant compared with the wild type indicates that W323 is essential for maintaining the stability BIR3-Smac-peptide complex.     

Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases

Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell-free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell-derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.