Global trend in exosome isolation and application: an update concept in management of diseases.

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, which will help us better understand their biological function. The strengths and limitations of conventional strategies and novel methods (microfluidic) for EV isolation are outlined in this review. We also present various exosome isolation techniques and kits that are commercially available and assess the global market demand for exosome assays.

CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice.

Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.

The role of miRNAs in the regulation of autophagy in autoimmune diseases.

Autoimmune diseases (AD), which are classified as chronic injuries, are caused by a specific auto-reactive reaction. The etiology of most ADs is not well understood. Meanwhile, Autophagy is a protective response defining as a catabolic method by lysosomes tending to maintain homeostasis acts by recycling and discrediting cell compartments. Autophagy plays a crucial role in controlling immune homeostasis by eliminating intracellular pathogens and presenting antigens to immune cognition. MicroRNAs are commonly known as endogenous non-coding small RNAs, which span 18-25 nt and take part in the gene expression at the post-transcriptional level regulation. miRNAs play important roles in different processes like, cell differentiation, duplicating, and apoptosis. Moreover, miRNAs are the critical molecules for the regular function of the immune system by modulating immune tolerance mechanisms and autoimmunity. Recent findings support the role of dysregulated miRNAs in the pathogenesis of ADs and in the regulation of autophagy. In this review, we will focus on the role of the miRNAs in the regulation of autophagy and then will explain the role of dysregulated miRNAs in the initiation of the ADs by modulating autophagy.