Search Results (3,341)

The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic physiological environments and intricate anatomical structures. Innovative drug delivery approaches are necessary to facilitate the precise regulation and manipulation of biological tissues. Nanotechnology is increasingly considered to manage reproductive system disorders, for example, nanomaterial imaging allows for early detection and enhances diagnostic precision to determine disease severity and progression. Additionally, nano drug delivery systems are gaining attention for their ability to target the reproductive system successfully, thereby increasing therapeutic efficacy and decreasing side effects. This comprehensive review outlines the anatomy of the female upper genital tract by highlighting the complex mucosal barriers and their impact on systemic and local drug delivery. Advances in nano drug delivery are described for their sustainable therapeutic action and increased biocompatibility to highlight the potential of nano drug delivery strategies in managing female upper genital tract disorders. Full article

Alzheimer’s disease (AD) is a common neurodegenerative disorder that presents a significant health concern, often leading to substantial cognitive decline among older adults. A prominent feature of AD is progressive dementia, which eventually disrupts daily functioning and the ability to live independently. A major challenge in addressing AD is its prolonged pre-symptomatic phase, which makes early detection difficult. Moreover, the disease’s complexity and the inefficiency of current diagnostic methods impede the development of targeted therapies. Therefore, there is an urgent need to enhance diagnostic methodologies for detection and treating AD even before clinical symptoms appear. Exosomes are nanoscale biovesicles secreted by cells, including nerve cells, into biofluids. These exosomes play essential roles in the central nervous system (CNS) by facilitating neuronal communication and thus influencing major physiological and pathological processes. Exosomal cargo, particularly microRNAs (miRNAs), are critical mediators in this cellular communication, and their dysregulation affects various pathological pathways related to neurodegenerative diseases, including AD. This review discusses the significant roles of exosomal miRNAs in the pathological mechanisms related to AD, focusing on the promising use of exosomal miRNAs as diagnostic biomarkers and targeted therapeutic interventions for this devastating disease. Full article

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis. Full article

Mutual interaction between doxorubicin (DOX) and cardiomyocytes is crucial for cardiotoxicity progression. Cardiomyocyte injury is an important pathological feature of DOX-induced cardiomyopathy, and its molecular pathogenesis is multifaceted. In addition to the direct toxic effects of DOX on cardiomyocytes, DOX-induced exosomes in the extracellular microenvironment also regulate the pathophysiological states of cardiomyocytes. However, the mechanisms by which DOX regulates exosome secretion and subsequent pathogenesis remain incompletely understood. Here, we found that DOX significantly increased exosome secretion from cardiomyocytes, and inhibiting this release could alleviate cardiomyocyte injury. DOX promoted exosome secretion by reducing cardiomyocyte silencing information regulator 1 (SIRT1) expression, exacerbating cardiotoxicity. DOX impaired lysosomal acidification in cardiomyocytes, reducing the degradation of intracellular multivesicular bodies (MVBs), resulting in an increase in MVB volume before fusing with the plasma membrane to release their contents. Mechanistically, SIRT1 loss inhibited lysosomal acidification by reducing the expression of the ATP6V1A subunit of the lysosomal vacuolar-type H+ ATPase (V-ATPase) proton pump. Overexpressing SIRT1 increased ATP6V1A expression, improved lysosomal acidification, inhibited exosome secretion, and thereby alleviated DOX-induced cardiotoxicity. Interestingly, DOX also induced mitochondrial-derived vesicle formation in cardiomyocytes, which may further increase the abundance of MVBs and promote exosome release. Collectively, this study identified SIRT1-mediated impairment of lysosomal acidification as a key mechanism underlying the increased exosome secretion from cardiomyocytes induced by DOX, providing new insights into DOX-induced cardiotoxicity pathogenesis. Full article

Extracellular vesicles (EVs) are bilayer vesicles released by cells in the microenvironment of the liver including parenchymal and non-parenchymal cells. They are the third important mechanism in the communications between cells, besides the secretion of cytokines and chemokines and the direct cell-to-cell contact. The aim of this review is to discuss the important role of EVs in viral liver disease, as there is increasing evidence that the transportation of viral proteins, all types of RNA, and viral particles including complete virions is implicated in the pathogenesis of both viral cirrhosis and viral-related hepatocellular carcinoma. The biogenesis of EVs is discussed and their role in the pathogenesis of viral liver diseases is presented. Their use as diagnostic and prognostic biomarkers is also analyzed. Most importantly, the significance of possible novel treatment strategies for liver fibrosis and hepatocellular carcinoma is presented, although available data are based on experimental evidence and clinical trials have not been reported. Full article

Deep caries and severe periodontitis cause bone resorption in periodontal tissue, and severe bone resorption leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are important for the healing of defective periodontal tissue. It is increasingly understood that healing of periodontal tissue is mediated through the secretion of trophic factors, particularly exosomes. This study investigated the effects of exosomes from human PDLSCs (HPDLSCs-Exo) on human osteoblast-like cells in vitro and on the healing of rat calvarial bone defects in vivo. HPDLSCs-Exo were isolated and characterized by their particle shape, size (133 ± 6.4 nm), and expression of surface markers (CD9, CD63, and CD81). In vitro results showed that HPDLSCs-Exo promoted the migration, mineralization, and expression of bone-related genes such as alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), osteocalcin (OCN), and osteopontin (OPN) in human osteoblast-like cells. Furthermore, in vivo results showed that more newly formed bone was observed in the HPDLSCs-Exo-treated group than in the non-treated group at the defect sites in rats. These results indicated that HPDLSCs-Exo could promote osteogenesis in vitro and in vivo, and this suggests that HPDLSCs-Exo may be an attractive treatment tool for bone healing in defective periodontal tissue. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and memory loss. While the precise causes of AD remain unclear, emerging evidence suggests that messenger RNA (mRNA) dysregulation contributes to AD pathology and risk. This study examined exosomal mRNA expression profiles of 15 individuals diagnosed with AD and 15 healthy controls from Barranquilla, Colombia. Utilizing advanced bioinformatics and machine learning (ML) techniques, we identified differentially expressed mRNAs and assessed their predictive power for AD diagnosis and AD age of onset (ADAOO). Our results showed that ENST00000331581 (CADM1) and ENST00000382258 (TNFRSF19) were significantly upregulated in AD patients. Key predictors for AD diagnosis included ENST00000311550 (GABRB3), ENST00000278765 (GGTLC1), ENST00000331581 (CADM1), ENST00000372572 (FOXJ3), and ENST00000636358 (ACY1), achieving > 90% accuracy in both training and testing datasets. For ADAOO, ENST00000340552 (LIMK2) expression correlated with a delay of ~12.6 years, while ENST00000304677 (RNASE6), ENST00000640218 (HNRNPU), ENST00000602017 (PPP5D1), ENST00000224950 (STN1), and ENST00000322088 (PPP2R1A) emerged as the most important predictors. ENST00000304677 (RNASE6) and ENST00000602017 (PPP5D1) showed promising predictive accuracy in unseen data. These findings suggest that mRNA expression profiles may serve as effective biomarkers for AD diagnosis and ADAOO, providing a cost-efficient and minimally invasive tool for early detection and monitoring. Further research is needed to validate these results in larger, diverse cohorts and explore the biological roles of the identified mRNAs in AD pathogenesis. Full article

Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the L. fermentum KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including interleukin (IL)-20, IL-8, IL-6, and IL-1B, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including TJP1, TJP2, and occludin-1, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of IL1B, IL20, IL6, IL8, and NFAT5 in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut–eye axis communication via exosomes. Full article

Diabetic retinopathy (DR) is a salient cause of blindness worldwide. There is still an immense need to understand the pathophysiology of DR to discover better diagnostic and therapeutic modalities. Human retinal endothelial cells (HRECs) were treated with 15-HETE or D-glucose, then miRNAs were isolated, and a microarray was performed. MirWALK 2 and Ingenuity Pathway Analysis (IPA) were used to analyze the microarray results. Exosomal miRNAs from 15-HETE-treated HRECs were isolated, microarrayed, and then imported into IPA for further analysis. The microarray results showed that 15-HETE downregulated 343 miRNAs and upregulated 297 miRNAs in HRECs. High glucose treatment induced a differential expression of HREC-miRNAs where 185 miRNAs were downregulated and 244 were upregulated. Comparing the impact of 15-HETE versus DG or diabetic mouse retina elaborated commonly changing miRNAs. Pathway and target analysis for miRNAs changed in 15-HETE-treated HRECs revealed multiple targets and pathways that may be involved in 15-HETE-induced retinal endothelial dysfunction. The HREC-exosomal miRNAs were differentially expressed after 15-HETE treatment, with 34 miRNAs downregulated and 45 miRNAs upregulated, impacting different cellular pathways. Here, we show that 15-HETE induces various changes in the cellular and exosomal miRNA profile of HRECs, highlighting the importance of targeting the 12/15 lipoxygenase pathway in DR. Full article

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder, and urinary exosomal microRNAs (miRNAs) were utilized as potential disease prediction or diagnostic biomarkers in numerous studies. This study investigated the differential expression of urinary exosomal miRNAs between non-diabetes mellitus (NDM) individuals and those with T2DM. Aim: To elucidate the association between urinary exosomal miRNAs and T2DM. Methods: We recruited patients diagnosed with T2DM and NDM individuals in West China Hospital, Sichuan University, from November 2023 to February 2024. Subsequently, we performed sequencing of urinary exosomal microRNAs in both groups. The obtained sequencing results were further validated using RT-qPCR in both the training set and the validation set. Additionally, we conducted logistic regression analysis and Spearman correlation analysis on miRNAs with significant differential expression, as well as analysis of their biological functions. Results: A total of 118 urine samples were collected, 59 from individuals diagnosed with T2DM and 59 from NDM. There were differentially expressed miR-183-5p (p = 0.034) and miR-125a-5p (p = 0.008) between the two groups. Furthermore, multivariate regression analysis demonstrated that higher miR-125a-5p levels were negatively associated with the risk of T2DM (p = 0.044; OR: 0.046; 95% CI: 0.002, 0.922). Bioinformatics analysis indicated that the target genes of miR-183-5p were predominantly involved in insulin signaling and glucose transport processes, while those target genes of miR-125a-5p primarily mediated autophagy. Conclusions: miR-183-5p and miR-125a-5p might be involved in the pathogenesis of T2DM, while higher urinary exosomal miR-125a-5p was negatively associated with the risk of T2DM. Full article

Since the discovery that exosomes can exchange genes, their potential use as tools for tissue regeneration, disease diagnosis, and therapeutic applications has drawn significant attention. Emerging three-dimensional (3D) printing technologies, such as bioprinting, which allows the printing of cells, proteins, DNA, and other biological materials, have demonstrated the potential to create complex body tissues or personalized 3D models. The use of 3D spheroids in bioprinting facilitates volumetric tissue reconstruction and accelerates tissue regeneration via exosome secretion. In this review, we discussed a convergence approach between two promising technologies for bioprinting and exosomes in regenerative medicine. Among the various 3D cell culture methods used for exosome production, we focused on spheroids, which are suitable for mass production by bioprinting. We then summarized the research results on cases of bioprinting applications using the spheroids and exosomes produced. If a large number of spheroids can be supplied through bioprinting, the spheroid-exosome-based bioprinting technology will provide new possibilities for application in tissue regeneration, disease diagnosis, and treatment. Full article

Excessive exposure to manganese (Mn) increases the risk of chronic neurological diseases, including Parkinson’s disease (PD) and other related Parkinsonisms. Aggregated α-synuclein (αSyn), a hallmark of PD, can spread to neighboring cells by exosomal release from neurons. We previously discovered that Mn enhances its spread, triggering neuroinflammatory and neurodegenerative processes. To better understand the Mn-induced release of exosomal αSyn, we examined the effect of Mn on endosomal trafficking and misfolded protein degradation. Exposing MN9D dopaminergic neuronal cells stably expressing human wild-type (WT) αSyn to 300 μM Mn for 24 h significantly suppressed protein and mRNA expression of Rab11a, thereby downregulating endosomal recycling, forcing late endosomes to mature into multivesicular bodies (MVBs). Ectopic expression of WT Rab11a significantly mitigated exosome release, whereas ectopic mutant Rab11a (S25N) increased it. Our in vitro and in vivo studies reveal that Mn exposure upregulated (1) mRNA and protein levels of endosomal Rab27a, which mediates the fusion of MVBs with the plasma membrane; and (2) expression of the autophagosomal markers Beclin-1 and p62, but downregulated the lysosomal marker LAMP2, thereby impairing autophagolysosome formation as confirmed by LysoTracker, cathepsin, and acridine orange assays. Our novel findings demonstrate that Mn promotes the exosomal release of misfolded αSyn by impairing endosomal trafficking and protein degradation. Full article

Disturbances in carbohydrate metabolism are suggested to be the early symptoms of pancreatic ductal adenocarcinoma (PDAC). The accumulated data suggests that endocrine function-related biomarkers may represent a breakthrough in the early detection of PDAC. Factors which may predispose one to the development of PDAC are insulin resistance and hyperinsulinemia. Elevated insulin levels induce the onset of carcinogenesis by altering the differentiation and function of islet cells through stimulating growth factors, including insulin-like growth factors (IGFs). Impaired β cell function, along with the impact of PDAC-released factors (e.g., adrenomedullin (ADM), IGF-1, and macrophage inhibitory factor (MIF) on pancreatic islets, may contribute to the induction of diabetes associated with PDAC. Recently, exosomes have attracted worldwide attention due to their role in varied features of cell function, particularly in cancer progression. Exosomes comprise of small extracellular vesicles produced by almost all cells. These vesicles contain a vast array of biomolecules, including proteins and microRNAs. Exosomes participate in cancer growth and promote angiogenesis. They promote tumorigenesis and metastasis, and are associated with the acquisition of cancer cells resistant to chemotherapy. Data have been accumulating recently on the role of exosomes in the rapid recognition, prognosis and potential therapy of pancreatic cancer. Full article

In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (TB) cells transport small RNA and other informational biomolecules from the placenta to the brain where their contents have pleiotropic effects. Here, EVs were isolated from the medium in which human trophoblasts (TBs) had been differentiated in vitro from induced pluripotent stem cells (iPSC) and from cultured iPSC themselves, and their small RNA content analyzed by bulk RNA-seq. EVs derived from human TB cells possess unique profiles of miRs, including hsa-miR-0149-3p, hsa-302a-5p, and many long non-coding RNAs (lncRNAs) relative to EVs isolated from parental iPSC. These miRs and their mRNA targets are enriched in neural tissue. Human neural progenitor cells (NPCs), generated from the same iPSC, were exposed to EVs from either TB or iPSC controls. Both sets of EVs were readily internalized. EVs from TB cells upregulate several transcripts in NPCs associated with forebrain formation and neurogenesis; those from control iPSC upregulated a transcriptional phenotype that resembled glial cells more closely than neurons. These results shed light on the possible workings of the placenta–brain axis. Understanding how the contents of small RNA within TB-derived EVs affect NPCs might yield new insights, possible biomarkers, and potential treatment strategies for neurobehavioral disorders that originate in utero, such as autism spectrum disorders (ASDs). Full article

Plant-derived exosome-like nanoparticles (PELNs) are a type of membranous vesicle isolated from plant tissues. They contain proteins, lipids, nucleic acids, and other components. PELNs are involved in the defensive response to pathogen attacks by exerting anti-inflammatory, antiviral, antifibrotic, and antitumor effects through the substances they contain. Most PELNs are edible and can be used as carriers for delivering specific drugs without toxicity and side effects, making them a hot topic of research. Sources of PELNs are abundantly, and they can be produced in high yields, with a low risk of developing immunogenicity in vivo. This paper summarizes the formation, isolation, and purification methods; physical properties; and composition of PELNs through a comprehensive literature search. It also analyzes the biomedical applications of PELNs, as well as future research directions. This paper provides new ideas and methods for future research on PELNs. Full article