جستجوی مقالات مرتبط با کلیدواژه « exosome » در نشریات گروه « پزشکی »

Exosomes are tiny vesicles that cells secrete into the extracellular environment. They are crucial in cellular communication and have wide-ranging physiological and pathological ramifications. Cargo sorting, MVB development and maturation, MVB transport, and MVB fusion with the plasma membrane are the four essential steps in exosome biogenesis. The high heterogeneity of exosomes is due to the fact that each process is modulated by the competition or coordination of multiple mechanisms, resulting in the sorting of diverse compositions of molecular cargos into different subpopulations of exosomes. In cancer, exosomes have been shown to play a crucial role in tumor growth, metastasis, and pre-metastatic niche formation. In this mini-review, we briefly compile what we know about exosomes at present, including how they are made, what they carry, and how they promote tumor growth. Exosomes' potential as diagnostic and prognostic biomarkers is discussed. We also take a look at the research that hasn't been done and the challenges that have been overlooked.

Leishmania is a vector-borne protozoon, which causes visceral, cutaneous and mucocutaneous leishmaniosis in human and animals. Monocyte- derived exosome vaccines can be used as prophylaxis and immunotherapy strategies. The aim of this study was to design a multiple-epitope candidate vaccine using leishmaniolysin (GP63) and rK39 proteins against Leishmania major and L. infantum for monocyte-derived exosome preparation.

This study was carried out in Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran, 2023–2024. Effective immunodominant epitopes were selected from two antigenic proteins of GP63 and rK39 using various immunoinformatics and bioinformatics approaches. Vibrio cholerae β- subunit was used as an adjuvant to stimulate immune responses. Then, appropriate linkers were selected for the fusion of epitopes. The 3D model of candidate vaccine was predicted and validated.

This designed candidate vaccine could effectively be used as a prophylaxis strategy against leishmaniosis.

A candidate vaccine was designed using bioinformatic and immunoinformatic studies with virtual acceptable quality; however, effectiveness of this vaccine should be verified through further in-vitro and in-vivo studies.

Nervous and brain cells injury is a complex, life-threatening condition that causes mortality and disability worldwide. Noeffective treatment has been clinically verified to date. Achieving effective drug delivery across the blood–brain barrier (BBB) presents a major challenge to therapeutic drug development for nervous and brain cells injury. Furthermore, the field of nerve damage biomarkers is rapidly developing to cope with the many aspects of pathology and enhance clinical management of this type of damage. Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence types of stem cells differentiation. Exosomes are endogenous extracellular vehicles (EVs) containing various biological materials, including lipids, proteins, microRNAs, and other nucleic acids. Compelling evidence exists that Exos, such as stem cell-derived Exos and even neuron or glial cell-derived Exos, are promising treatment strategies for Nervous cells injury because they pass through the BBB and have the potential to deliver molecules to target lesions. Meanwhile, Exos have Fewer safety risks compared to intravenous injection or orthotopic transplantation of viable cells, such as microvascular occlusion or imbalanced growth of transplanted cells. These unique characteristics also make Exos contents, especially Exos-derived microRNAs, as appealing biomarkers in nervous and brain cells injury. In this review, we explore the potential impact of cell-derived Exos and exosome-derived contents on the diagnosis, therapy, and prognosis prediction of nerve damage. The associated challenges and opportunities are also discussed.

MicroRNAs (miRNAs) are small non-coding RNAs that function in all biological processes. Recent findings suggest that exosomes, which are small vesicles abundantly secreted by various cell types, can transport miRNAs to target cells. Here, we elucidated the effect of miRNA-loaded exosomes on lipopolysaccharide (LPS)-induced inflammation in H9c2 cardiomyocytes.

Exosomes were isolated from mesenchymal stem cells (MSC) and loaded with miR-412-5p. Additionally, the effect of the miR-412-5p-loaded exosomes on LPS-induced inflammation in H9c2 cardiomyocytes was evaluated by assessing the levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling factors was evaluated using reverse transcription-quantitative PCR and western blotting.

miR-412-5p-loaded exosomes inhibited LPS-induced secretion of inflammatory mediators (NO, PGE2, and ROS), pro-inflammatory cytokines (IL-1β and IL-6), and COX-2 and iNOS expression. Additionally, miR-412-5p-loaded exosomes significantly decreased the expression of MAPK signaling molecules, including p-extracellular signal-regulated kinase (ERK), p-p38, and p-Jun kinase (JNK), in H9c2 cardiomyocytes.

These findings showed that miR-412-5p-loaded exosomes ameliorated LPS-induced inflammation in H9c2 cardiomyocytes by inhibiting COX-2 and iNOS expression, inflammatory mediators, and pro-inflammatory cytokines via the MAPK pathway. The findings indicate that miR-412-5p-loaded exosomes may be effective for the prevention of myocardial injury.

Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton’s Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells.

MicroRNAs (miRNAs) have crucial roles in human cancers. Many studies have certified that miRNAs are implicated in tumor progression via exosomes. Nevertheless, whether miRNA-339 is derived by exosomes and its effects in gastric cancer (GC) presents obscure. Therefore, our study attempted to clarify the functional role and molecular mechanism of miRNA-339 in GC.

In this research, the potential of miRNA-339 in GC was verified through miRNA-339 elevation with cell function assays. Bioinformatics analysis together with mechanical assay was implemented for assessing the regulatory relation between miRNA-339 and zinc finger protein 689 (ZNF689). Moreover, the existence of exosomes was determined via transmission electron microscopy together with nanoparticle tracking analysis.

miRNA-339 presented significant down-regulation in GC. miRNA-339 elevation suppressed GC cell proliferation, invasion along with migration while elevated GC cell apoptosis. miRNA-339 targeted ZNF689 3’UTR to repress ZNF689 expression, thereby hindering GC progression. Finally, miRNA-339 was majorly incorporated into exosomes to hinder GC progression.

In summary, exosome-delivered miRNA-339 may act to be a tumor repressor in GC by targeting ZNF689, which might be an underlying therapeutic target for GC.

Exosomes are nanovesicular vehicles capable of transporting different cargoes. Based on their characteristics, exosomes are proposed as a class of vehicles for targeted delivery of therapeutics. We aimed to establish a HEK293T stable cell line capable of secreting GRP78-specific scFv-targeted exosomes.

The pLEX-LAMP2b-GRP78 construct was developed by enzymatic replacement of DARPin in pLEX-LAMP2b-DARPin with a GRP78-specific scFv. pLEX-LAMP2b-GRP78 (or TurboGFP as control), psPAX2, and pMD2.G plasmids were co-transfected into HEK293T cells, and produced lentiviruses were harvested. Different multiplicities of infection (MOI; 10, 20, 30, 60, 120, and 240) were used for the transduction of HEK293T to select the most appropriate one as assessed by flow cytometry. Transduced HEK293T cells were subject to puromycin selection and the presence of the scFv was assessed in the established cell line at the DNA, transcript, and protein levels by PCR, RT-PCR, and Western blotting, respectively.

pLEX-LAMP2b-GRP78 was successfully developed. Co-transfection resulted in the expression of GFP by HEK293T in the control group 48 hours following transfection. The MOI of 60 was selected as 10% of cells were GFP+ 72 hours following transduction. Following puromycin selection, the presence of the integrated scFv DNA and transcript was confirmed. Moreover, Western blotting results confirmed the presence of the His-tagged scFv in the established cell line.

HEK293T cells can be engineered for the production of targeted exosomes which could be applied for therapeutic purposes. Moreover, scFvs are potent targeting domains that could be leveraged for the development of targeted exosomes.

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways.  Exosomes derived from heat‐shocked tumor cells (HS‐TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS‐TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS‐TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that  DCs treated with HS‐TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS‐TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS‐TEXs could be used as a strategy to improve DC maturation and activation.

Exosomes, a subset of extracellular vesicles (EVs), are crucial for intercellular communication in various contexts. Despite their small size, they carry diverse cargo, including RNA, proteins, and lipids. Internalization by recipient cells raises concerns about potential disruptions to cellular functions. Notably, the ability of exosomes to traverse the blood-brain barrier (BBB) has significant implications.

To conduct a thorough investigation into the existing academic literature on exosomes within the framework of neuron-glia communication, a comprehensive search strategy was implemented across the PubMed, Google Scholar, and Science Direct databases. Multiple iterations of the keywords "exosome," "neuron-glia communication," and "neurological disorders" were employed to systematically identify relevant publications. Furthermore, an exploration of the Clinicaltrials. gov database was undertaken to identify clinical trials related to cellular signaling, utilizing analogous terminology.

Although the immediate practical applications of exosomes are somewhat limited, their potential as carriers of pathogenic attributes offers promising opportunities for the development of precisely targeted therapeutic strategies for neurological disorders. This review presents a comprehensive overview of contemporary insights into the pivotal roles played by exosomes as agents mediating communication between neurons and glial cells within the central nervous system (CNS).

By delving into the intricate dynamics of exosomal communication in the CNS, this review contributes to a deeper understanding of the roles of exosomes in both physiological and pathological processes, thereby paving the way for potential therapeutic advancements in the field of neurological disorders.

 Seminal plasma exosomes are now recognized to play a complex role in the regulation of the female reproductive system infertility. The objective of this study was to assess the effect of exosomes derived from the sperm of men with oligoasthenoteratozoospermia on endometrial implantation-related genes.

To isolate the exosomes, we employed an ultracentrifugation method on samples derived from 10 fertile men with normal sperm parameters and 10 men with oligoasthenoteratozoospermia. The size distribution and ultrastructure of the exosomes were then characterized using transmission electron microscopy and dynamic light scattering. We detected an exosome marker using western blot analysis and confirmed the cytoplasmic localization of the exosomes by incubating them with DiI dye and visualizing them using fluorescence microscopy. After 6 hours of in vitro treatment of endometrial epithelial cells with 100 µg/ml seminal exosome, the endometrial receptivity genes were examined using qRT-PCR. To perform data analysis and quantification, we utilized Image J and Prism software. P< 0.05 were considered statistically significant.

After 6 hours of treatment, the mRNA levels of MUC1, LIF, G-CSF, CX3CL1, and VEGF were significantly downregulated in the endometrial epithelial cells treated with oligoasthenoteratozoospermia exosomes compared to the normal group. Although changes were observed in the mean mRNA levels of IL8 and TGF-ß genes in the oligoasthenoteratozoospermia group compared to the normal group, these differences did not reach statistical significance (p > 0.05).

Oligoasthenoteratozoospermia exosomes have a distinct effect on endometrial receptivity compared to normal exosomes, leading to reduced expression of implantation-related genes.

 Exosomes are natural nanoparticles that participate in intercellular communication through molecular transport. Recently, due to their membrane vesicular structure and surface proteins, exosomes have been used extensively in the research field of drug delivery. Osteoporosis is an inflammation in which the cellular balance of bone tissue is disturbed that reduces bone density and making bone prone to abnormal fractures with small amount of force. Utilizing estrogen is one of the main therapeutic strategies for osteoporosis. Despite the positive effects of estrogen on bone tissue, changes in the natural estrogen levels of the body can cause a number of diseases such as different types of cancer. Therefore, designing a therapeutic system which controls more accurate tissue targeting of estrogen seems to be a rational and promising practical approach.

 In this study, bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes were loaded by estradiol using two different methods of drug loading, namely incubation and sonication methods and then the survival effects of the drug loaded exosomes on BMMSCs was investigated.

 Examination of size, shape, and surface factors of exosomes in different states (pure exosomes and drug-loaded exosomes) showed that the round morphology of exosomes was preserved in all conditions. However, the particles size increased significantly when loaded by sonication method. The increased survival of BMMSCs was noted with estradiol-loaded exosomes when compared to the control group.

 The results suggest that estradiol-loaded exosomes have potential to be used as nano-drug carriers in the treatment of osteoporosis.

The purpose of this study was to assess the effects of exosomes derived from dental pulp mesenchymal stem cells (DPSCs) on the viability of odontoblast cells. Exosomes were extracted from human DPSC cells via ultracentrifugation. Scanning electron microscopy and western blot analysis for CD9 and CD81 demonstrated characteristics of exosomes. Developing odontoblasts were exposed to increasing concentrations of exosomes (10-400 ng/ml) over time periods of 24, 48, 72, and 96 hours. Cell viability was evaluated using MTT assays. In addition, real-time PCR was used to assess expression levels of Wnt, beta-catenin, PI3K, Akt, Bcl-2, and Bax in cells after 24-96 hours of exposure to 100 and 400 ng/ml exosomes. Odontoblast viability was found to be enhanced by DPSC-derived exosomes, with greater impacts at higher concentrations and time periods of 72-96 hours. Expression of PI3K, AKT, Wnt, beta-catenin, and Bcl-2 were notably upregulated in odontoblasts following 96 hours of DPSC-exosome treatment. Conversely, Bax expression was significantly downregulated. These findings suggest DPSC-exosomes promote odontoblast survival through modulated expression of genes involved in key survival pathways over extended exposure periods. Our findings demonstrated that exosomes derived from DPSC cells possess innate nanoparticle properties, leading to enhanced survival of odontoblast cells. This effect is achieved through the activation of the Wnt/beta-catenin and P3K/AKT signaling pathways, ultimately resulting in an increased Bcl-2/Bax ratio.

Exosomes are among the factors whose importance has been shown in many diseases today. Recently, it has been shown that exosomes play an important role in the pathogenesis of Intrauterine Growth Restriction (IUGR); however, few studies have been conducted in this regard.

The articles in this review study were retrieved from some databases including PubMed, Google scholar, and Scopus. All the included articles were in English, and those in other languages were excluded. Search keywords included IUGR, exosome, pathogenesis, Mechanism, Cell Signaling, Oxidative Stress, Inflammation, and Endothelial Dysfunction.

Studies have shown that exosomes contain factors, molecules and gene activators that affect molecular pathways regulation. These molecules play an important role in regulating inflammatory reactions, oxidative stress, and production of Reactive Oxygen Species (ROS). The activation of these pathways can aggravate the clinical symptoms of IUGR. In addition, exosomes can impress induction or inhibition of endothelial dysfunction, which leads to the development of IUGR. Hence, identifying upstream and downstream pathways helps design therapeutic strategies to treat patients.

This study focused on preparing a multiscale three-dimensional (3D) scaffold using tricalcium phosphate nanoparticles (triCaPNPs) in a substrate of poly(acrylic acid) (PAA) polymer for controlled release of exosomes in bone tissue engineering.

A scaffold was fabricated with a material mixture containing acrylic acid (AA) monomer, N,N’-methylenebisacrylamide (MBAA), ammonium persulfate (APS), sodium bicarbonate (SBC), and triCaPNPs called composite scaffold (PAA/triCaPNPs) via cross-linking and freezedrying methods. The synthesis process was easy and without complex multi-steps. Through mimicking the hybrid (organic-inorganic) structure of the bone matrix, we here chose triCaPNPs for incorporation into the PAA polymer. After assessing the physicochemical properties of the scaffold, the interaction of the scaffold with human umbilical cord mesenchymal stem cells (UCMSCs) such as attachment, proliferation, and differentiation to osteoblast cells was evaluated. In addition, we used DiI-labeled exosomes to verify the exosome entrapment and release from the scaffold.

The polymerization reaction of 3D scaffold was successful. Based on results of physicochemical properties, the presence of nanoparticles in the composite scaffold enhanced the mechanical stiffness, boosted the porosity with a larger pore size range, and offered better hydrophilicity, all of which would contribute to greater cell penetration, proliferation, and then better bone differentiation. In addition, our results indicated that our scaffold could take up and release exosomes, where the exosomes released from it could significantly enhance the osteogenic commitment of UC-MSCs.

The current research is the first study fabricating a multiscale scaffold using triCaPNPs in the substrate of PPA polymer using a cross-linker and freeze-drying process. This scaffold could mimic the nanoscale structure and chemical combination of native bone minerals. In addition, our results suggest that the PAA/triCaPNPs scaffold could be beneficial to achieve controlled exosome release for exosome-based therapy in bone tissue engineering.