Adipose tissue fibrosis, characterized by abnormal extracellular matrix deposition within adipose tissue, signifies a crucial indicator of adipose tissue malfunction, potentially leading to organ tissue dysfunction. Various factors, including a high-fat diet, non-alcoholic fatty liver disease, and insulin resistance, coincide with adipose tissue fibrosis. MicroRNAs (miRNAs) represent a class of small non-coding RNAs with significant influence on tissue fibrosis through diverse signaling pathways. For instance, in response to a high-fat diet, miRNAs can modulate signaling pathways such as TGF-β/Smad, PI3K/AKT, and PPAR-γ to impact adipose tissue fibrosis. Furthermore, miRNAs play roles in inhibiting fibrosis in different contexts: suppressing corneal fibrosis via the TGF-β/Smad pathway, mitigating cardiac fibrosis through the VEGF signaling pathway, reducing wound fibrosis via regulation of the MAPK signaling pathway, and diminishing fibrosis post-fat transplantation via involvement in the PDGFR-β signaling pathway. Notably, the secretome released by miRNA-transfected adipose-derived stem cells facilitates targeted delivery of miRNAs to evade host immune rejection, enhancing their anti-fibrotic efficacy. Hence, this study endeavors to elucidate the role and mechanism of miRNAs in adipose tissue fibrosis and explore the mechanisms and advantages of the secretome released by miRNA-transfected adipose-derived stem cells in combating fibrotic diseases.

Cancer remains a prominent worldwide health concern, presenting existing therapies with frequent difficulties, including major toxicity, limited effectiveness, and treatment resistance emergence. These issues highlight the necessity for novel and enhanced remedies. Exosomes, tiny extracellular vesicles that facilitate intercellular communication, have attracted interest for their potential medicinal applications. Carrying a variety of molecules, including microRNAs, small interfering RNAs, long non-coding RNAs, proteins, lipids, and DNA, these vesicles are positioned as promising cancer treatment options. Current studies have increasingly investigated the capacity of microRNAs as a strategic approach for combating malignancy. Mesenchymal stem cells (MSC) are recognized for their aptitude to augment blood vessel formation, safeguard against cellular death, and modulate immune responses. Consequently, researchers examine exosomes derived from MSCs as a safer, non-cellular choice over therapies employing MSCs, which risk undesirable differentiation. The focus is shifting towards employing miRNA-encapsulated exosomes sourced from MSCs to target and heal cancerous cells selectively. However, the exact functions of miRNAs within MSC-derived exosomes in the context of cancer are still not fully understood. Additional exploration is necessary to clarify the role of these miRNAs in malignancy progression and to pinpoint viable therapeutic targets. This review offers a comprehensive examination of exosomes derived from mesenchymal stem cells, focusing on the encapsulation of miRNAs, methods for enhancing cellular uptake and stability, and their potential applications in cancer treatment. It also addresses the difficulties linked to this methodology and considers future avenues, including insights from current clinical oncology research.

While primary breast cancer (BC) is often effectively managed, metastasis remains the primary cause of BC-related fatalities. Gaps remain in our understanding of the mechanisms regulating cancer cell organotropism with predilection to specific organs. Unraveling mediators of site-specific metastasis could enhance early detection and enable more tailored interventions. Liquid biopsy represents an innovative approach in cancer involving the analysis of biological materials such as circulating tumor DNA and tumor-derived extracellular vesicles (EV) found in body fluids like blood or urine. This offers valuable insights for characterizing and monitoring tumor genomes to advance personalized medicine in metastatic cancers.

We performed in-depth analyses of EV cargo associated with BC metastasis using eight murine cell line models with distinct metastatic potentials and organotropism to the lung, the bone, the liver, and the brain. We characterized the secretome of these cells to identify unique biomarkers specific to metastatic sites.

Small EVs isolated from all cell lines were quantified and validated for established EV markers. Tracking analysis and electron microscopy revealed EV secretion patterns that differed according to cell line. Cell-free (cf)DNA and EV-associated DNA (EV-DNA) were detected from all cell lines with varying concentrations. We detected a TP53 mutation in both EV-DNA and cfDNA. Mass spectrometry-based proteomics analyses identified 698 EV-associated proteins, which clustered according to metastatic site. This analysis highlighted both common EV signatures and proteins involved in cancer progression and organotropism unique to metastatic cell lines. Among these, 327 significantly differentially enriched proteins were quantified with high confidence levels across BC and metastatic BC cells. We found enrichment of specific integrin receptors in metastatic cancer EVs compared to EVs secreted from non-transformed epithelial cells and matched tumorigenic non-metastatic cells. Pathway analyses revealed that EVs derived from parental cancer cells display a cell adhesion signature and are enriched with proteins involved in cancer signaling pathways.

Taken together, the characterization of EV cargo in a unique model of BC organotropism demonstrated that EV-DNA and EV proteomes were informative of normal and cancer states. This work could help to identify BC biomarkers associated with site-specific metastasis and new therapeutic targets.

Gastrointestinal cancers are prevalent malignant neoplasms in clinical medicine. The development of drug resistance in gastrointestinal cancers result in tumor recurrence and metastasis and greatly diminish the efficacy of treatment. Exosomes, as the shuttle of intercellular molecular cargoes in tumor micro-environment, secreted from tumor and stromal cells mediate drug resistance by regulating epithelial-mesenchymal transition, drug efflux, stem-like phenotype and cell metabolism. Meanwhile, exosomes have already received tremendous attention in biomedical study as potential drug resistant biomarkers as well as treatment strategy in gastrointestinal cancers. Primary challenge to implement this potential is the ability to obtain high-grade exosomes efficiently; however, exosomes lack standard protocols for their processing and characterization. Furthermore, this field suffers from insufficient standardized reference materials and workflow for purification, detection and analysis of exosomes with defined biological properties. This review summarize the unique biogenesis, composition and novel detection methods of exosomes and informed the underlying correlation between exosomes and drug resistance of gastrointestinal cancers. Moreover, the clinical applications of exosomes are also summarized, might providing novel therapy for the individual treatment of gastrointestinal cancers.

Hepatocellular carcinoma (HCC) remains one of the major threats to human health worldwide. The emergence of systemic therapeutic options has greatly improved the prognosis of patients with HCC, particularly those with advanced stages of the disease. In this review, we discussed the pathogenesis of HCC, genetic alterations associated with the development of HCC, and alterations in the tumor immune microenvironment. Then, important indicators and emerging technologies related to the diagnosis of HCC are summarized. Also, we reviewed the major advances in treatments for HCC, offering insights into future prospects for next-generation managements.

Modern advancements in medicine include developing targeted drug delivery systems in the medical field, which are designed to unravel the potential of therapeutic products and overcome the barriers to the effectiveness of current approaches. Various nanopolymer carrier systems have been introduced in this regard, and the simple characteristics of extracellular vesicles have drawn special attention to their application as an effective drug delivery tool. Exosomes are very similar to transport vesicles and have a lipid-biomembrane covering an aqueous core. They also contain both hydrophilic and lipophilic substances and deliver their cargo to the desired targets. These properties enable exosomes to overcome some of the limitations of liposomes. Exosomes can easily diffuse into body fluids and remain in the bloodstream for a long time, crossing physiological barriers and entering cells. Exosomes, which contain a large volume of biomolecules, do not stimulate immune responses and do not accumulate in the liver or lungs instead of target tissues. Recent advancements in regenerative medicine have enabled scientists to utilize exosomes extracted from mesenchymal stem cells (MSCs), which possess significant regenerative abilities, for treating various diseases. The contents of these exosomes are crucial for both diagnosis and treatment, as they influence disease progression. Numerous in vitro studies have confirmed the safety, effectiveness, and therapeutic promise of exosomes in conditions such as cancer, neurodegenerative disorders, cardiovascular issues, and orthopedic ailments. This article explores the therapeutic potential of MSC-derived exosomes and outlines the essential procedures for their preparation.

Mesenchymal stem cells (MSCs) are currently being used in clinical trials for the treatment of a wide range of diseases and have a wide range of applications in the fields of tissue engineering and regeneration. Exosomes are extracellular vesicles containing a variety of components such as proteins, nucleic acids and lipids, which are widely present in biological fluids and have the functions of participating in intercellular information transfer, immune response and tissue repair, and can also be used as carriers to target and deliver tumors to improve therapeutic effects. Mesenchymal stem cell-derived Exosomes (MSC-Exos), which have the advantages of low immunogenicity and high tumor homing ability, have attracted much attention in targeted drug delivery. Here, we review the current knowledge on the involvement of MSC-Exos in tumor progression and their potential as drug delivery systems in targeted therapies. It also discusses the advantages and prospects of MSC-Exos as a drug carrier and the challenges that still need to be overcome.

The chemical carcinogen diethylnitrosamine (DEN) is often used to induce HCC in mice. Curiously, several labs have reported that the removal of oncoproteins from hepatocytes exacerbated DEN-induced HCC, with mechanisms unknown. This study aimed at deciphering molecular mechanisms underlying the tumor suppressive effect of oncoproteins.

We generated mutant mouse lines with hepatocyte-specific deletions of Met , Ptpn11 / Shp2 , Ikkβ , or Ctnnb1/β-catenin and assessed DEN-induced tumorigenesis in the wild-type and mutant mice. To systematically examine genetic and molecular signaling alterations, we performed whole exome and RNA-sequencing on liver samples collected at the pre-cancer and established cancer stages. Although the mutational profiles of DEN-induced tumors were barely different in wild-type and mutant mice, oncoprotein ablation increased DEN-induced mutational burdens, especially in Shp2-deficient tumors. RNA-sequencing revealed multiple changes in signaling pathways, in particular, upregulated epithelial-mesenchymal transition, cell migration, and tumor metastasis, as well as downregulated small molecule metabolism that was affected by oncoprotein ablation. We identified key molecules and pathways that are associated with hepatic innate immunity and implicated in liver tumorigenesis. In addition, we unveiled markedly changed expression of a few miRNAs in the human HCC database.

The aggravation of DEN-induced HCC progression seen on oncoprotein ablation could be caused by common and distinct genomic and signaling alterations. This study reveals a new level of complexity in hepatocarcinogenesis and elucidates molecular mechanisms underlying tumor evolution and recurrence.

Cancer continues to pose a global threat despite potent anticancer drugs, often accompanied by undesired side effects. To enhance patient outcomes, sophisticated multifunctional approaches are imperative. Small extracellular vesicles (EVs), a diverse family of naturally occurring vesicles derived from cells, offer advantages over synthetic carriers. Among the EVs, the exosomes are facilitating intercellular communication with minimal toxicity, high biocompatibility, and low immunogenicity. Their tissue-specific targeting ability, mediated by surface molecules, enables precise transport of biomolecules to cancer cells. Here, we explore the potential of exosomes as innovative therapeutic agents, including cancer vaccines, and their clinical relevance as biomarkers for clinical diagnosis. We highlight the cargo possibilities, including nucleic acids and drugs, which make them a good delivery system for targeted cancer treatment and contrast agents for disease monitoring. Other general aspects, sources, and the methodology associated with therapeutic cancer applications are also reviewed. Additionally, the challenges associated with translating exosome-based therapies into clinical practice are discussed, together with the future prospects for this innovative approach.

Exosomes are actively produced extracellular vesicles, released from different cell types, that exert important regulatory roles in vital cellular functions. Tumor-derived exosomes (TDEs) have received increasing attention because they enable intercellular communication between the neoplastic and non-neoplastic cells present in the microenvironment of tumors, affecting important functions of different types of mesenchymal stem cells (MSCs) with the ability to self-renew and differentiate. MSC-derived exosomes (MSC-exos) carry a variety of bioactive molecules that can interact with specific cellular targets and signaling pathways, influencing critical processes in tumor biology, and exhibiting properties that either promote or inhibit tumor progression. They can regulate the tumor microenvironment by modulating immune responses, enhancing or suppressing angiogenesis, and facilitating tumor cells' communication with distant sites, thus altering the behavior of non-cancerous cells present in the microenvironment. Herein, we explore the main functions of TDEs and their intricate interactions with MSC-exos, in terms of enhancing cancer progression, as well as their promising clinical applications as tumor microenvironment modulators.

Aim: Exosomes derived from adipose-derived stem cells (ASCs) in mice have been reported to influence immune regulation. Yet, the potential immunological effects of ASCs-derived exosomes and their interaction with lymphocytes during transplant immunity remain understudied. Methods: ASCs from BALB/c mice, along with their conditioned culture medium, were collected for the extraction, isolation, and comprehensive characterization of exosomes. Splenic cell suspensions were isolated from BALB/c mice and subsequently processed for downstream analyses. Lymphocytes were isolated via gradient centrifugation and stimulated in vitro with the purified exosomes to assess their functional responses. Lymphocyte proliferation was quantified using the CCK8 assay, and the relative frequencies of CD4+ T cells, CD8+ T cells, Treg cells, NK (natural killer) cells, macrophages, B cells, dendritic cells (DCs), and Th17 cells were determined through flow cytometric analysis. Before establishing the skin transplantation model, the mice were administered PBS, 0.5 × 108 exosomes, 1 × 108 exosomes, 1.5 × 108 exosomes, or ASCs via intravenous injection through the tail vein. Seven days after transplantation, the spleens, drainage lymph nodes, and blood samples were harvested for lymphocyte isolation and further downstream analyses. Results: Exosomes derived from ASCs significantly increased the CD4+/CD8+ ratio and Treg cell levels, without inducing any notable changes in Th17 cell content or CTLA-4 protein expression in CD4+ T cells. Compared to the PBS-treated group, both ASC and exosome treatment groups demonstrated an enhanced CD4+/CD8+ ratio, increased Treg cell content, and elevated CTLA-4 protein expression in spleen tissue following skin transplantation, while Th17 cell levels remained unaffected. Compared to the ASC treatment group, the exosome group exhibited a higher CD4+/CD8+ ratio and Treg cell levels, alongside a reduced proportion of PD-1+ Treg cells and lower CTLA-4 protein expression in CD3+CD4+ T cells. No significant differences were observed in the proportions of NK cells, macrophages, B cells, and DCs in the spleens across all treatment groups. In peripheral blood, an increased proportion of CD3+ T cells, macrophages, and DCs was detected, accompanied by a reduced proportion of NK cells and B cells. In the draining lymph nodes, no significant changes were observed in the proportions of CD3+ T cells and B cells, while macrophages, NK cells, and DCs showed elevated proportions. In the exosome-treated group, mouse grafts exhibited a disorganized and thinner granular layer, accompanied by focal regions of inflammatory cell infiltration. Both exosome and ASC treatments significantly extended the survival of skin grafts. Conclusion: Exosomes derived from ASCs promote lymphocyte proliferation and modulate their phenotypic profiles in mouse skin graft models, effectively extending graft survival.

High-dose methotrexate (HD-MTX) serves as the cornerstone of central nervous system lymphoma (CNSL) treatment, but its efficacy is limited due to low blood-brain barrier (BBB) penetration and adverse effects. This study is focused on an exosome-based drug delivery approach aimed at enhancing BBB permeability, thereby reducing the required dosage of methotrexate (MTX) while ensuring specific targeting of CNSL.

Human adipose-derived mesenchymal stem cells (hAMSCs) were modified with a lentiviral vector encoding anti-CD19, incorporated into exosomes characterized by colloidal gold immunoelectron microscopy and Nano flow cytometry. MTX loaded into anti-CD19-Exos via co-incubation, assessed for loading and encapsulation efficiencies using HPLC. In vitro BBB model constructed using hCMEC/D3 and astrocytes to investigate BBB permeability. In vivo efficacy of anti-CD19-Exo-MTX evaluated in intracranial CNSL models using MRI. Biodistribution tracked with DiR-labeled exosomes, drug concentration in CSF measured by HPLC. LC-MS/MS identified and characterized exosomal proteins analyzed using GO Analysis. Neuroprotective effects of exosomal proteins assessed with TUNEL and Nissl staining on hippocampal neurons in CNSL models. Liver and kidney pathology, blood biochemical markers, and complete blood count evaluated exosomal protein effects on organ protection and MTX-induced myelosuppression.

We generated anti-CD19-Exo derived from hAMSCs. These adapted exosomes effectively encapsulated MTX, enhancing drug accessibility within lymphoma cells and sustained intracellular accumulation over an extended period. Notably, anti-CD19-Exo-MTX interacted with cerebrovascular endothelial cells and astrocytes of the BBB, leading to endocytosis and facilitating the transportation of MTX across the barrier. Anti-CD19-Exo-MTX outperformed free MTX in vitro, exhibiting a more potent lymphoma-suppressive effect (P < 0.05). In intracranial orthotopic CNSL models, anti-CD19-Exo-MTX exhibited a significantly reduced disease burden compared to both the MTX and Exo-MTX groups, along with prolonged overall survival (P < 0.05). CSF drug concentration analysis demonstrated enhanced stability and longer-lasting drug levels for anti-CD19-Exo-MTX. Anti-CD19-Exo-MTX exhibited precise CNSL targeting with no organ toxicity. Notably, our study highlighted the functional potential of reversal effect of hAMSCs-exosomes on MTX-induced neurotoxicity, hepatic and renal impairment, and myelosuppression.

We present anti-CD19-Exo-MTX as a promising exosome-based drug delivery platform that enhances BBB permeability and offers specific targeting for effective CNSL treatment with reduced adverse effects.

Exosomes, spherical lipid-bilayered particles secreted by cells, have recently emerged as a novel and highly promising drug delivery system, attracting extensive attention in the field of biomedical research. Dendritic-cell-derived exosomes (DC-Exos) possess surface protein and ligands characteristic of DC cells, such as functional MHC-I and MHC-II, CD80, CD86. These components play a crucial role in immune responses, facilitating antigen uptake, presentation, and the activation of antigen-specific CD4 and CD8 T cells. These properties make them striking and excellent drug delivery vehicles for use in various immune diseases and cancer therapy. This review summarizes and discusses the characteristics, current methods and types of drug loading of DC-Exos. Its surface modifications and application in disease treatment were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

Recently, increasing interest has been in utilizing mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially exosomes, as nanocarriers for miRNA delivery in cancer treatment. Due to such characteristics, nanocarriers are specific: biocompatible, low immunogenicity, and capable of spontaneous tumor accumulation. MSC-EVs were loaded with therapeutic miRNAs and minimized their susceptibility to degradation by protecting the miRNA from accessibility to degrading enzymes and providing targeted delivery of the miRNAs to the tumor cells to modulate oncogenic pathways. In vitro and in vivo experiments suggest that MSC-EVs loaded with miRNAs may inhibit tumor growth, prevent metastasis, and increase the effectiveness of chemotherapy and radiotherapy. However, these improvements present difficulties such as isolation, scalability, and stability of delivered miRNA during storage. Furthermore, the issues related to off-target effects, as well as immunogenicity, can be a focus. The mechanisms of miRNA loading into MSC-EVs, as well as their targeting efficiency and therapeutic potential, can be outlined in this manuscript. For the final part of the manuscript, the current advances in MSC-EV engineering and potential strategies for clinical application have been described. The findings of MSC-EVs imply that they present MSC-EVs as a second-generation tool for precise oncology.

Patients with colorectal cancer (CRC) harboring BRAF mutation have a poor prognosis. The median survival time for patients with advanced BRAFV600E-mutant CRC is only approximately one year. Owing to the insensitivity to standard chemotherapy, there are still no effective and highly specific treatment strategies available in clinical practice for CRC patients with BRAF mutation. Therefore, targeting the BRAFV600E mutation site, researching and exploring novel targeted therapies are essential to improve the survival rate of patients with this CRC subtype.

This study aims to develop a precise therapeutic system for BRAFV600E CRC, based on the carrier properties of extracellular vesicles (EVs) and gene therapy targeting BRAFV600E.

We first obtained engineered cells capable of stably producing EVs loaded with BRAFV600E nucleic acid drugs (siBRAFV600E). Next, BRAFV600E-mutant and wild-type CRC cell lines, as well as corresponding subcutaneous and metastasis models, were used to evaluate the therapeutic efficacy of EVs-siBRAFV600E and explored the mechanism. Notably, patient-derived xenograft (PDX) models, which share the same molecular characteristics, pathological features, and heterogeneity as patients do, were utilized to further explore the therapeutic efficacy and mechanisms.

EVs-siBRAFV600E specifically inhibited BRAFV600E CRC but didn't affect BRAF wild-type CRC in vitro and vivo. EVs-siBRAFV600E exerts its therapeutic effect by regulating the MEK1/2-ERK1/2 pathway, and it has demonstrated excellent therapeutic efficacy in PDX models.

The therapeutic EVs we constructed are effective and specific for the BRAFV600E-mutant CRC. This study provides a novel strategy for the treatment of CRC patients with BRAFV600E mutation.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. As a chronic inflammatory disease with a complicated pathophysiology marked by abnormal lipid metabolism and arterial plaque formation, atherosclerosis is a major contributor to CVDs and can induce abrupt cardiac events. The discovery of exosomes' role in intercellular communication has sparked a great deal of interest in them recently. Exosomes are involved in strategic phases of the onset and development of atherosclerosis because they have been identified to control pathophysiologic pathways including inflammation, angiogenesis, or senescence. This review investigates the potential role of stem cell-derived exosomes in atherosclerosis management. We briefly introduced atherosclerosis and stem cell therapy including stem cell-derived exosomes. The biogenesis of exosomes along with their secretion and isolation have been elaborated. The design engineering of exosomes has been summarized to present how drug loading and surface modification with targeting ligands can improve the therapeutic and targeting capacity of exosomes, demonstrating atheroprotective action. Moreover, the mechanism of action (endothelial dysfunction, reduction of dyslipidemia, macrophage polarization, vascular calcification, and angiogenesis) of drug-loaded exosomes to treat atherosclerosis has been discussed in detail. In the end, a comparative and balanced viewpoint has been given regarding the current challenges and potential solutions to advance exosome engineering for cardiovascular therapeutic applications.

Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.

Glioma is one of the most prevalent primary intracranial tumors, and biomarker testing offers a non-invasive modality with high diagnostic efficiency. The aim of this meta-analysis is to evaluate the diagnostic effectiveness of exosomes as biomarkers for glioma. We included 16 studies on exosomes as biomarkers for gliomas. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for 25 biomarkers across these 16 studies were as follows: 82% (95% CI: 0.77-0.86), 91% (95% CI: 0.86-0.94), 9.10 (95% CI: 5.64-14.68), 0.20 (95% CI: 0.16-0.25), 45.94 (95% CI: 25.40-83.09), and 0.92 (95% CI: 0.89-0.94), respectively. Meta-regression indicated that biomarker analysis, biomarker type, and sample size may be sources of heterogeneity. Subgroup analysis suggested that ultracentrifugation (UC) was a better method for extracting exosomes. miRNA and other RNA groups (sncRNA, lncRNA, circRNA) provided higher SEN (0.88 vs. 0.84 vs. 0.78) compared to proteins. This study demonstrates the superior diagnostic efficacy of exosomes as biomarkers for gliomas, with high accuracy in diagnosing gliomas.

The diagnostic performance of liquid biopsy-based biomarkers for HCC was comprehensively compared in this network meta-analysis (NMA).

A thorough literature search was conducted to identify all comparative studies from January 1, 2000, to January 11, 2024. The QUADAS-2 tool was utilized to appraise the quality of studies involving diagnostic performance. R (v4.3.3) and an ANOVA model-based NMA were used to assess the diagnostic accuracy of each biomarker.

This study included 82 studies comprising a total of 15,024 patients.CircRNA demonstrated significantly superior performance in distinguishing HCC from healthy populations (superiority index: 3.550 (95% CI [0.143-3])) compared to other diagnostic biomarkers for HCC. "mRNA exhibited significantly superior performance in distinguishing HCC from liver disease patients (superiority index:10.621 (95% CI [7-11])) compared to other diagnostic biomarkers for HCC. Further subgroup analysis of the top-ranking liquid biopsy-based diagnostic biomarkers revealed that hsa_circ_000224 (superiority index: 3.091 (95% CI[0.143-9]) ranked remarkably higher in distinguishing HCC from both healthy populations and liver disease patients. Subgroup analysis of mRNA demonstrated that KIAA0101 mRNA (superiority index: 2.434 (95% CI [0.2-5]) ranked remarkably higher in distinguishing HCC from healthy populations and liver disease patients, respectively.

The results of this meta-analysis show that circRNA and mRNA are the first choice for HCC diagnosis. Subsequent analysis of circRNA and mRNA highlighted hsa_circ_000224, hsa_circ_0003998, KIAA0101 mRNA and GPC-3mRNA as the optimal diagnostic biomarkers for distinguishing HCC from healthy populations and liver disease patients, respectively. Well-structured prospective studies are crucial to comprehensively validate these findings.

https://www.crd.york.ac.uk/PROSPERO/,identifier CRD42024521299.

Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes. This study demonstrated that AGD1, derived from prostate cancer stem cells (PCSCs), enhanced the stemness of prostate cancer cells and reduced the therapeutic effect of docetaxel in CRPC.

Quantitative real-time PCR (qPCR) was employed to determine the expression levels of AGD1 and METTL13 mRNAs in PCSCs and exosomes. Protein expression levels were examined using western blots and dot blots. The potential functions of AGD1 and METTL13 in CRPC were investigated through cell proliferation assay, Transwell assay, EdU incorporation assays, Annexin V-FITC/PI staining, and sphere formation assays. To uncover the underlying mechanisms of AGD1, RNA pull-down assay, RIP, co-Immunoprecipitation (co-IP), mass spectrometry (MS), Methylated RNA immunoprecipitation (MeRIP) and single-base elongation and ligation-based qPCR amplification method (SELECT) were performed. The effects of AGD1 and METTL13 on CRPC development and metastasis under docetaxel treatment were analyzed using a xenograft mouse model and an organoid model. Additionally, liposomal-chitosan nanocomplex drug delivery systems were designed to explore AGD1's role in regulating docetaxel treatment resistance in CRPC.

AGD1 expression was upregulated in PCSCs and exosomes. Downregulating AGD1 enhanced the sensitivity of CRPC to docetaxel treatment by inhibiting their stemness, with the reverse also being true. RNA pull-down, combined with MS, co-IP and RIP assays, demonstrated that AGD1 binds to METTL13 and USP10, forming a complex that facilitates METTL13 protein accumulation through USP10-induced deubiquitination. MeRIP assay and SELECT assay revealed that METTL13 transcriptionally controls the mRNA decay of CD44 via m6A methylation. Additionally, this process activates the pSTAT3/PI3K-AKT signaling pathway. Organoid models and liposomal-chitosan nanocomplex drug delivery systems showed that reducing AGD1 expression enhanced the therapeutic effect of docetaxel in CRPC.

AGD1 mediates the stemness and apoptosis of PCSCs and promotes docetaxel treatment resistance by enhancing tumor growth and metastasis through USP10/METTL13-mediated CD44 mRNA decay in CRPC.

This review highlights recent progress in exosome-based drug delivery for cancer therapy, covering exosome biogenesis, cargo selection mechanisms, and their application across multiple cancer types. As small extracellular vesicles, exosomes exhibit high biocompatibility and low immunogenicity, making them ideal drug delivery vehicles capable of efficiently targeting cancer cells, minimizing off-target damage and side effects. This review aims to explore the potential of exosomes in cancer therapy, with a focus on applications in chemotherapy, gene therapy, and immunomodulation. Additionally, challenges related to exosome production and standardization are analyzed, highlighting the importance of addressing these issues for their clinical application. In conclusion, exosome-based drug delivery systems offer promising potential for future cancer therapies. Further research should aim to enhance production efficiency and facilitate clinical translation, paving the way for innovative cancer treatment strategies.

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, with a high rate of disability and mortality. Due to the complicated pathological process of SCI, there is no effective clinical treatment strategy at present. Although mesenchymal stem cells (MSCs) are effective in the treatment of SCI, their application is limited by factors such as low survival rate, cell dedifferentiation, tumorigenesis, blood-brain barrier, and immune rejection. Fortunately, there is growing evidence that most of the biological and therapeutic effects of MSCs may be mediated by the release of paracrine factors, which are extracellular vesicles called exosomes. Exosomes are small endosomal vesicles with bilaminar membranes that have recently been recognized as key mediators for communication between cells and tissues through the transfer of proteins, lipids, nucleic acids, cytokines, and growth factors. Mesenchymal stem cell-derived exosomes (MSC-exos) play a critical role in SCI repair by promoting angiogenesis and axonal growth, regulating inflammation and immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be used to transport genetic material or drugs to target cells, and their relatively small size allows them to permeate the blood-brain barrier. Studies have demonstrated that some exosomal miRNAs derived from MSCs play a significant role in the treatment of SCI. In this review, we summarize recent research advances in MSC-exos and exosomal miRNAs in SCI therapy to better understand this emerging cell-free therapeutic strategy and discuss the advantages and challenges of MSC-exos in future clinical applications.

Chemotherapy and radiotherapy (chemo-/radiotherapy) have advanced as the main treatment modalities for nasopharyngeal carcinoma (NPC), improving patient survival rates. However, chemo-/radiotherapy resistance in NPC cells has emerged as a key factor contributing to poor prognosis. Recently, competing endogenous RNA networks (ceRNETs) have garnered attention for their potential clinical value in studying chemo-/radiotherapy resistance. In this review, we aimed to explore the molecular mechanisms of ceRNA-related molecules, including circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and other competing endogenous RNAs, in regulating the chemo-/radiotherapy resistance in NPC. Additionally, we discuss the potential applications of ceRNA as a prognostic indicator and therapeutic target for this resistance.

Gastrointestinal tumors present a significant challenge for precision medicine due to their complexity, necessitating the development of more specific diagnostic tools and therapeutic agents. Recent advances have positioned coding and non-coding RNAs as emerging biomarkers for these malignancies, detectable by liquid biopsies, and as innovative therapeutic agents. Many RNA-based therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO), have entered clinical trials or are available on the market. This review provides a narrative examination of the diagnostic and therapeutic potential of RNA in gastrointestinal cancers, with an emphasis on its application in precision medicine. This review discusses the current challenges, such as drug resistance and tumor metastasis, and highlights how RNA molecules can be leveraged for targeted detection and treatment. Additionally, this review categorizes specific diagnostic biomarkers and RNA therapeutic targets based on tissue type, offering a comprehensive analysis of their role in advancing precision medicine for gastrointestinal tumors.

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Despite recent advancements, clinical outcomes for GC remain unsatisfactory. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown promise in inhibiting tumor progression, but their role in GC, specifically human umbilical cord MSC-derived small EVs (hucMSC-sEVs), is not well understood. This study investigates the therapeutic potential of hucMSC-sEVs in GC treatment. We found that hucMSC-sEVs are captured by GC cells, substantially inhibiting their proliferation and inducing apoptosis. MiRNA sequencing revealed that hucMSC-sEVs were enriched with miRNAs having anticancer properties. Among these, miR-13896, a new miRNA, was identified as a potent inhibitor of GC cell proliferation and a promoter of apoptosis. Mechanistic studies revealed that miR-13896 targets and down-regulates the ATG2A-mediated autophagy pathway, suppressing GC cell growth and metastasis. Furthermore, we enriched hucMSC-sEVs with miR-13896 through electroporation. These engineered EVs specifically targeted tumor sites and significantly reduced GC cell growth and migration in vitro and in vivo. MiR-13896 emerged as a promising therapeutic target for GC. The delivery of miR-13896 via hucMSC-sEVs represents a novel and effective strategy for GC treatment, highlighting the potential of EV-based therapies to combat this malignancy.

Mesenchymal stem cells (MSCs) have shown a great potential role in treating liver injury. MSCs can promote liver regeneration by differentiating into hepatocytes, and can also secrete exosomes to participate in the repair of liver injury. Increasing evidence has shown that mesenchymal stem cell-derived exosomes (MSC-EXOs) play an important role in treating liver injury. In this review, the biogenesis and function of exosomes and the characteristics of MSC-EXOs were analyzed based on recent research results. MSC-EXOs are significant in liver injuries such as liver fibrosis, liver failure, hepatocellular carcinoma, oxidative stress, and lipid steatosis, and participate in the process of liver regeneration.

The primary objective of this study was to closely monitor and identify adverse events (AEs) associated with Sorafenib, a pharmacological therapeutic agent used to treat hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer. The ultimate goal was to optimize patient safety and provide evidence-based guidance for the appropriate use of this drug.

Reports from the FDA Adverse Event Reporting System (FAERS) database were comprehensively collected and analyzed, covering the first quarter of 2004 to the first quarter of 2024. Disproportionality analysis was performed using robust algorithms for effective data mining to quantify the signals associated with Sorafenib-related AEs.

In total, we identifued 18,624 patients (82,857 AEs in the Sorafenib population) from the collected reports and examined, the occurrence of Sorafenib-induced AEs in 26 organ systems. The study results revealed the presence of the expected AEs, including Diarrhoea, Palmar-plantar erythrodysaesthesia syndrome, Hepatocellular carcinoma, Fatigue, and Rash, which was consistent with the information provided in the drug insert. In addition, unexpected significant AEs, such as Gait inability, Palmoplantar keratoderma and Hyperkeratosis were observed at the preferred term (PT) level. These findings suggest the potential occurrence of adverse reactions not currently documented in drug descriptions.

This study successfully detected new and unforeseen signals associated with Sorafenib-related AEs related to Sorafenib administration, providing important insights into the complex correlations between AEs and Sorafenib use. The results of this study emphasize the critical importance of continuous and vigilant surveillance for the timely identification and effective management of AEs to improve the overall patient safety and wellbeing in the context of Sorafenib therapy.

Drug resistance is a major challenge in cancer therapy that often leads to treatment failure and disease relapse. Despite advancements in chemotherapeutic agents and targeted therapies, cancers often develop drug resistance, making these treatments ineffective. Extracellular vesicles (EVs) have gained attention for their potential applications in drug delivery because of their natural origin, biocompatibility, and ability to cross biological barriers. Using the unique properties of EVs could enhance drug accumulation at target sites, minimize systemic toxicity, and precisely target specific cells. Here, we discuss the characteristics and functionalization of EVs, the mechanisms of drug resistance, and the applications of engineered EVs to overcome drug resistance. This review provides a comprehensive overview of the advancements in EV-based drug delivery systems and their applications in overcoming cancer drug resistance. We highlight the potential of EV-based drug delivery systems to revolutionize cancer therapy and offer promising strategies for more effective treatment modalities.

Exosomes are vesicles produced by the human body for carrying certain information from one cell to another. The carriers are nanosized vesicles carrying a wide variety of cargo like RNA, DNA, and proteins. Exosomes are also being used in the early diagnosis of various diseases and disorders. Current research focuses on exosomes tailoring for achieving therapeutic potential in various diseases and disorders. Besides this, their biocompatibility, stability, adjustable efficacy, and targeting properties make them attractive vehicles for formulation developers. Various preclinical studies suggested that the exosome culture cells are also modified with certain genes to achieve the desirable properties of resultant exosomes. The human body also produces some other vesicles like Ectosomes and Exomeres produced along with exosomes. Additionally, vesicles like Migrasomes are produced by migrating cells and apoptotic bodies, and Oncosomes are produced by cancer cells which can also be useful for the diagnosis of various diseases and disorders. For the separation of desired exosomes from other vesicles some latest techniques that can be useful viz differential centrifugation, density gradient centrifugation, and immunoaffinity purification have been discussed. Briefly, this review summarized various techniques of isolation of purified exosomes along with an overview of the application of exosomes in various neurodegenerative disorders and cancer along with various latest aspects of exosomes in disease progression and management which might be beneficial for the researchers.

Mesenchymal stem cells (MSCs) are a class of protocells that can differentiate into various cell types and have robust replication and renewal capabilities. MSCs secrete various nutritional factors to regulate the microenvironment of tumor tissues. The mechanism by which they inhibit or promote tumor growth may be closely related to MSC-derived exosomes (MSC-Exo). However, the role of MSC-Exo vesicles in tumors remains controversial. This review discusses the potential applications of microRNAs in exosomes derived from MSCs in treating tumors.

Liver cancer is the third leading cause of cancer-related mortality worldwide. HCC, the most common type of primary liver cancer, is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally occurring small noncoding RNAs, play crucial roles in HCC by simultaneously modulating the expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as noninvasive diagnostic tools. Restoring or inhibiting specific miRNAs has offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into the dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in the proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, the immune microenvironment in HCC, and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC.

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.

Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer and the third leading cause of cancer mortality globally. Despite surgical resection being the preferred approach for early-stage HCC, most patients are diagnosed at intermediate to advanced stages, limiting treatment options to chemotherapy and immunotherapy, which often yield poor outcomes. Extracellular vesicles (EVs), minute lipid-bilayered particles released by diverse cells under various physiological and pathological conditions, are crucial for mediating communication between cells. Mounting evidence indicates that EVs sourced from different cells can profoundly influence the HCC tumor microenvironment (TME), thereby affecting the progression of HCC. Given their immunogenicity and liver-targeting properties, these EVs not only hold promise for HCC treatment but also provide avenues for advancing early diagnostic methods and assessing prognosis. This review not only describes the function of EVs within the HCC tumor microenvironment but also analyzes their therapeutic advantages and explores their significance in various therapeutic approaches for HCC, including chemotherapy, immunotherapy, combination therapy, and their role as innovative drug delivery carriers. Furthermore, it highlights the potential of EVs as biomarkers for the diagnosis and prognosis of HCC.

The aim is to explore the clinical effects of combined treatment of Traditional Chinese Medicine (TCM) and western medicine in viral hepatitis B cirrhosis and the effects on microRNA (miR)-122 and miR-200a. 116 patients with chronic hepatitis B cirrhosis were admitted to our hospital. Real-time fluorescent quantitative PCR (qPCR) was employed to reveal the level of serum miR-122 and miR-200a in the three groups. The clinical effects of the two groups were compared, including alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL) and alpha fetoprotein (AFP) indexes, coagulation function indexes, liver elasticity value and the main therapeutic effects. After treatment, the ALT, AST, TBIL and AFP indexes significantly decreased in both groups, which were much lower in the western medicine (WM) + TCM Group. The levels of albumin (ALB) all increased, and the increase was more significant in the WM + TCM Group. The prothrombin time (PT) was down-regulated while the prothrombin activity (PTA) was up-regulated in both groups. Both groups showed a decrease in liver elasticity after treatment, which was more obvious in the WM + TCM Group. The incidence of primary peritonitis, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding and electrolyte disturbance in the WM + TCM Group was significantly lower than those in the WM Group. The combination of Chinese and western medicine in the treatment of cirrhosis can reduce the occurrence of complications, improve the clinical symptoms and improve the clinical effects effectively, which is worthy of further study and clinical popularization. Viral hepatitis B, Liver cirrhosis, Combination of TCM and Western medicine, miR-122, miR-200a.

The global obesity epidemic, attributed to sedentary lifestyles, unhealthy diets, genetics and environmental factors, has led to over 1.9 billion adults being classified as overweight and 650 million living with obesity. Despite advancements in early detection and treatment, lung cancer prognosis remains poor due to late diagnoses and limited therapies. The obesity paradox challenges conventional thinking by suggesting that individuals with obesity and certain diseases, including cancer, may have an improved prognosis compared with their counterparts of a normal weight. This observation has prompted investigations to understand protective mechanisms, including potentially favorable adipokine secretion and metabolic reserves that contribute to tolerating cancer treatments. However, understanding the association between obesity and lung cancer is complex. While smoking is the primary risk factor of lung cancer, obesity may independently impact lung cancer risk, particularly in non‑smokers. Adipose tissue dysfunction, including low‑grade chronic inflammation, and hormonal changes contribute to lung cancer development and progression. Obesity‑related factors may also influence treatment responses and survival outcomes in patients with lung cancer. The impact of obesity on treatment modalities such as chemotherapy, radiotherapy and surgery is still under investigation. Challenges in managing patients with obesity and cancer include increased surgical complexity, higher rates of postoperative complications and limited treatment options due to comorbidities. Targeted interventions aimed at reducing obesity prevalence and promoting healthy lifestyles are crucial for lung cancer prevention. The impact of obesity on lung cancer is multifaceted and requires further research to elucidate the underlying mechanisms and develop personalized interventions for prevention and treatment.

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.

Hepatocellular carcinoma (HCC) poses a significant global health challenge due to its poor prognosis and limited therapeutic modalities. Anoikis and ErbB signaling pathways are pivotal in cancer cell proliferation and metastasis, but their relevance in HCC remains insufficiently explored.

This study evaluates the prognostic significance of anoikis and ErbB signaling pathways in HCC by utilizing data from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), three additional independent validation cohorts, and an in-house cohort. Advanced bioinformatics analyses and 167 machine learning models based on leave-one-out cross-validation (LOOCV) were used to predict HCC prognosis and assess outcomes of immune-targeted therapies. Additionally, key biological processes of the anoikis and ErbB signaling pathways in HCC were further investigated.

The single sample Gene Set Enrichment Analysis revealed a strong correlation between upregulated ErbB signaling in high anoikis-expressing tumors and poor clinical outcomes. The development of the Anoikis-ErbB Related Signature (AERS) using the LASSO + RSF model demonstrated robust predictive capabilities, as validated across multiple patient cohorts, and proved effective in predicting responses to immune-targeted therapies. Further investigation highlighted activated NOTCH signaling pathways and decreased macrophage infiltration was associated with resistance to sorafenib and immune checkpoint inhibitors, as evidenced by bulk and single-cell RNA sequencing (scRNA-seq).

AERS provides a novel tool for clinical prognosis and paves the way for immune-targeted therapeutic approaches, underscoring the potential of integrated molecular profiling in enhancing treatment strategies for HCC.