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.     

Melatonin,a toll-like receptor inhibitor: Current status and future perspectives

Toll-like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti-inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders.     

The role of microRNAs involved in PI3-kinase signaling pathway in colorectal cancer

In recent decades, cancer has been one of the most important concerns of the human community, which affects human life from many different ways, such as breast, lung, colorectal, prostate, and other cancers. Colorectal cancer is one of the most commonly diagnosed cancers in the world that has recently been introduced as the third leading cause of cancer deaths in the world. microRNAs have a very crucial role in tumorgenesis and prevention of cancer, which plays a significant role with influencing various factors through different signaling pathways. Phosphoinositide 3 (PI3)-kinase/AKT is one of the most important signaling pathways involved in the control and growth of tumor in colorectal cancer, through important proteins of this pathway, such as PTEN and AKT, that they can perform specific influence on this process. Our effort in this study is to collect microRNAs that act as tumor suppressors and oncomirs in this cancer through PI3-kinase/AKT signaling pathway.     

Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.     

A cell surface protein controls endocrine ring gland morphogenesis and steroid production

Identification of signals for systemic adaption of hormonal regulation would help to understand the crosstalk between cells and environmental cues contributing to growth, metabolic homeostasis and development. Physiological states are controlled by precise pulsatile hormonal release, including endocrine steroids in human and ecdysteroids in insects. We show in Drosophila that regulation of genes that control biosynthesis and signaling of the steroid hormone ecdysone, a central regulator of developmental progress, depends on the extracellular matrix protein Obstructor-A (Obst-A). Ecdysone is produced by the prothoracic gland (PG), where sensory neurons projecting axons from the brain integrate stimuli for endocrine control. By defining the extracellular surface, Obst-A promotes morphogenesis and axonal growth in the PG. This process requires Obst-A-matrix reorganization by Clathrin/Wurst-mediated endocytosis. Our data identifies the extracellular matrix as essential for endocrine ring gland function, which coordinates physiology, axon morphogenesis, and developmental programs. As Obst-A and Wurst homologs are found among all arthropods, we propose that this mechanism is evolutionary conserved.     

Impact of phosphorus application on drought resistant responses of Eucalyptus grandis seedlings

Eucalyptus grandis is the most widely planted tree species worldwide and can face severe drought during the initial months after planting because the root system is developing. A complete randomized design was used to study the effects of two water regimes (well‐watered and water‐stressed) and phosphorus (P) applications (with and without P) on the morphological and physio‐biochemical responses of E. grandis. Drought had negative effects on the growth and metabolism of E. grandis, as indicated by changes in morphological traits, decreased net photosynthetic rates (P_n), pigment concentrations, leaf relative water contents (LRWCs), nitrogenous compounds, over‐production of reactive oxygen species (ROS) and higher lipid peroxidation. However, E. grandis showed effective drought tolerance strategies, such as reduced leaf area and transpiration rate (E), higher accumulation of soluble sugars and proline and a strong antioxidative enzyme system. P fertilization had positive effects on well‐watered seedlings due to improved growth and photosynthesis, which indicated the high P requirements during the initial E. grandis growth stage. In drought‐stressed seedlings, P application had no effects on the morphological traits, but it significantly improved the LRWC, P_n, quantum efficiency of photosystem II (F_v/F_m), chlorophyll pigments, nitrogenous compounds and reduced lipid peroxidation. P fertilization improved E. grandis seedling growth under well‐watered conditions but also ameliorated some leaf physiological traits under drought conditions. The effects of P fertilization are mainly due to the enhancement of plant N nutrition. Therefore, P can be used as a fertilizer to improve growth and production in the face of future climate change.     

Removal of methylene blue dye from aqueous solutions by natural clinoptilolite and clinoptilolite modified by iron oxide nanoparticles

Adsorption techniques are widely used to remove industrial wastewater contaminants, especially non-biodegradable colourants. In this study, Iranian zeolite clinoptilolite was synthesised using magnetic iron oxide as an inexpensive and efficient adsorbent. The results showed that using natural zeolite, the removal efficiency of 26.8.6% at pH?=?3 reached 48% at pH?=?9. However, the adsorption capacity of the modified clinoptilolite did not change by increasing pH; it ranged from 96.4% to 98.6%. Moreover, increase in the initial concentration of the dye did not have any effects on the removal efficacy of the modified clinoptilolite. Using natural zeolite, on the other hand, the adsorption capacity showed a significant decrease and reached less than 10% at the 200?mg/l dye concentration. At the optimal contact time of 45?min, the dye removal rate by the modified zeolite was more than 98% at the optimal dose of 0.5?g. Indeed, the adsorption isotherm complied with Freundlich equation. Overall, the results showed that in comparison to the natural zeolite, the adsorption capacity of the clinoptilolite modified by iron nanoparticles increased significantly due to the uniformity of the cavities and increase in the surface of the adsorbent.