Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

Single-cell multiomics analysis reveals cell/tissue-specific associations in bipolar disorder.

This study investigates the cellular origin and tissue heterogeneity in bipolar disorder (BD) by integrating multiomics data. Four distinct datasets were employed, including single-cell RNA sequencing (scRNA-seq) data (embryonic and fetal brain, n = 8, 1,266 cells), BD Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data (adult brain, n = 210), BD bulk RNA-seq data (adult brain, n = 314), and BD genome-wide association study (GWAS) summary data (n = 413,466). The integration of scRNA-seq data with multiomics data relevant to BD was accomplished using the single-cell disease relevance score (scDRS) algorithm. We have identified a novel brain cell cluster named ADCY1, which exhibits distinct genetic characteristics. From a high-resolution genetic perspective, glial cells emerge as the primary cytopathology associated with BD. Specifically, astrocytes were significantly related to BD at the RNA-seq level, while microglia showed a strong association with BD across multiple panels, including the transcriptome-wide association study (TWAS), ATAC-seq, and RNA-seq. Additionally, oligodendrocyte precursor cells displayed a significant association with BD in both ATAC-seq and RNA-seq panel. Notably, our investigation of brain regions affected by BD revealed significant associations between BD and all three types of glial cells in the dorsolateral prefrontal cortex (DLPFC). Through comprehensive analyses, we identified several BD-associated genes, including CRMP1, SYT4, UCHL1, and ZBTB18. In conclusion, our findings suggest that glial cells, particularly in specific brain regions such as the DLPFC, may play a significant role in the pathogenesis of BD. The integration of multiomics data has provided valuable insights into the etiology of BD, shedding light on potential mechanisms underlying this complex psychiatric disorder.

Accurate identification of genes associated with brain disorders by integrating heterogeneous genomic data into a Bayesian framework.

BACKGROUND: Genome-wide association studies (GWAS) have revealed many brain disorder-associated SNPs residing in the noncoding genome, rendering it a challenge to decipher the underlying pathogenic mechanisms. METHODS: Here, we present an unsupervised Bayesian framework to identify disease-associated genes by integrating risk SNPs with long-range chromatin interactions (iGOAT), including SNP-SNP interactions extracted from ∼500,000 patients and controls from the UK Biobank, and enhancer-promoter interactions derived from multiple brain cell types at different developmental stages. FINDINGS: The application of iGOAT to three psychiatric disorders and three neurodegenerative/neurological diseases predicted sets of high-risk (HRGs) and low-risk (LRGs) genes for each disorder. The HRGs were enriched in drug targets, and exhibited higher expression during prenatal brain developmental stages than postnatal stages, indicating their potential to affect brain development at an early stage. The HRGs associated with Alzheimer's disease were found to share genetic architecture with schizophrenia, bipolar disorder and major depressive disorder according to gene co-expression module analysis and rare variants analysis. Comparisons of this method to the eQTL-based method, the TWAS-based method, and the gene-level GWAS method indicated that the genes identified by our method are more enriched in known brain disorder-related genes, and exhibited higher precision. Finally, the method predicted 205 risk genes not previously reported to be associated with any brain disorder, of which one top-risk gene, MLH1, was experimentally validated as being schizophrenia-associated. INTERPRETATION: iGOAT can successfully leverage epigenomic data, phenotype-genotype associations, and protein-protein interactions to advance our understanding of brain disorders, thereby facilitating the development of new therapeutic approaches. FUNDING: The work was funded by the National Key Research and Development Program of China (2024YFF1204902), the Natural Science Foundation of China (82371482), Guangzhou Science and Technology Research Plan (2023A03J0659) and Natural Science Foundation of Guangdong (2024A1515011363).

Evaluating music education interventions for mental health in Chinese university student: a dual fuzzy analytic method.

This study addresses the growing anxiety and depression among Chinese university students by evaluating and ranking music education strategies to alleviate these issues. We integrates Fuzzy Analytic Hierarchy Process (FAHP) and Fuzzy Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). FAHP was utilized to determine the weight of factors such as academic pressures, social relationships, and cultural norms, while fuzzy TOPSIS ranked the effectiveness of music education interventions based on these weights. The results revealed that 'Mental health stigma' and 'Academic Pressures and Rigidity' are among the highest weighted factors, significantly impacting student anxiety. 'Music Appreciation and Music-Based Self-Care' emerged as the most effective strategy. These results highlight the importance of direct involvement in music-related activities for improving student mental health.

Ureido-Ionic Liquid Mediated Conductive Hydrogel: Superior Integrated Properties for Advanced Biosensing Applications.

Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long-term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self-adhesion, self-regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one-pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self-regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel  exhibited broad-spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real-time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

BACKGROUND: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. METHODS: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. RESULTS: Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. CONCLUSIONS: Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

Chemical constituent characterization and determination of Quisqualis fructus based on UPLC-Q-TOF-MS and HPLC combined with fingerprint and chemometric analysis.

Quisqualis fructus (QF) is a traditional Chinese medicine (TCM) that it has a long history in the therapeutic field of killing parasites, eliminating accumulation, and stopping diarrhea. However, the therapeutic material basis of QF is remaining ambiguous nowadays. The geographical origin differences of QF are also usually ignored in the process of medication. In this study, the alcohol-aqueous soluble constituents in QF from different origins were systematically characterized and accurately measured by ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography (HPLC) respectively. Chemometric analysis was performed for origin differentiation and screening of potential quality marker (Q-marker). Finally, A total of 106 constituents were tentatively characterized in positive and negative ion modes, including 29 fatty acids, 26 organic acids, 11 amino acids and derivatives, 10 glycosides, 9 alkaloids and derivatives, and 21 other constituents. QF from different origins were effectively distinguished and 16 constituents were selected as the potential Q-markers subsequently. Four representative components (trigonelline, adenosine, ellagic acid, and 3,3'-di-O-methylellagic acid) in QF samples were simultaneously determined. HPLC fingerprint analysis indicated that the similarity between 16 batches of QF was in the range of 0.870-0.999. The above results provide some insights for the research on the pharmacodynamic constituents, quality control, and geographical discrimination of QF.

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases.

Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers' understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.

Gastric cancer metastatic to the breast: A case report.

BACKGROUND: Metastatic breast cancer originating in the gastrointestinal tract is a rare occurrence. The limited number of cases has resulted in incomplete understanding of the disease, making it challenging to differentiate from primary breast cancer. While clinical history and immunohistochemical studies can aid in distinguishing between the two, the management principles and pathogenesis of gastrointestinal metastatic breast cancer remain controversial. The scarcity of data has hampered comprehensive knowledge. Our objective is to shed light on this rare disease through our case study. CASE SUMMARY: Here, we report a case of breast metastasis from gastric cancer in a 43-year-old woman. This patient was admitted to our hospital with complaints of discomfort in the upper and middle abdomen persisting for two months, as well as black stools for over ten days. She underwent radical distal gastrectomy for gastric cancer, followed by postoperative chemotherapy. Three years later, the patient developed bilateral breast nodules. Imaging studies indicated a high probability of malignancy. She subsequently underwent a right modified radical mastectomy and excision of a left breast mass. Postoperative pathology revealed the right breast tumor was consistent with primary gastric cancer. CONCLUSION: We present a case of breast metastasis from gastric cancer to contribute to the limited foundation of research into this rare disease.

An atlas of causal association between micronutrients and osteoarthritis.

OBJECTIVE: This study examines the causal relationships between serum micronutrients and site-specific osteoarthritis (OA) using Mendelian Randomization (MR). METHODS: This study performed a two-sample MR analysis to explore causal links between 21 micronutrients and 11 OA outcomes. These outcomes encompass overall OA, seven site-specific manifestations, and three joint replacement subtypes. Sensitivity analyses using MR methods, such as the weighted median, MR-Egger, and MR-PRESSO, assessed potential horizontal pleiotropy and heterogeneity. Genome-wide association summary statistical data were utilized for both exposure and outcome data, including up to 826,690 participants with 177,517 OA cases. All data was sourced from Genome-wide association studies datasets from 2009 to 2023. RESULTS: In the analysis of associations between 21 micronutrients and 11 OA outcomes, 15 showed Bonferroni-corrected significance (P < 0.000216), without significant heterogeneity or horizontal pleiotropy. Key findings include strong links between gamma-tocopherol and spine OA (OR = 1.70), and folate with hand OA in finger joints (OR = 1.15). For joint replacements, calcium showed a notable association with a reduced likelihood of total knee replacement (TKR) (OR = 0.52) and total joint replacement (TJR) (OR = 0.56). Serum iron was significantly associated with an increased risk of total hip replacement (THR) (OR = 1.23), while folate indicated a protective effect (OR = 0.95). Various sex-specific associations were also uncovered. CONCLUSION: These findings underscore the critical role of micronutrients in osteoarthritis, providing valuable insights for preventive care and potential enhancement of treatment outcomes.

Assembly of root-associated bacterial community and soil health in cadmium-contaminated soil affected by nano/bulk-biochar compost associations.

Biochar (BC) has been proven effective in promoting the production of safety food in cadmium (Cd)-polluted soil and the impact can be further enhanced through interaction with compost (CM). However, there existed unclear impacts of biochar with varying particle sizes in conjunction with compost on microbiome composition, rhizosphere functions, and soil health. Hence, in this study, two bulk-biochar derived from wood chips and pig manure were fabricated into nano-biochar using a ball-milling method. Subsequently, in a field experiment, the root-associated bacterial community and microbial functions of lettuce were evaluated in respond to Cd-contaminated soil remediated with nano/bulk-BCCM. The results showed that compared to bulk-BCCM, nano-BCCM significantly reduced the Cd concentration in the edible part of lettuce and the available Cd in the soil. Both nano-BCCM and bulk-BCCM strongly influenced the composition of bacterial communities in the four root-associated niches, and enhanced rhizosphere functions involved in nitrogen, phosphorus, and carbon cycling, as well as the relative abundance and biodiversity of keystone modules in rhizosphere soil. Furthermore, soil quality index analysis indicated that nano-BCCM exhibited greater potential than bulk-BCCM in maintaining soil health. The data revealed that nano-BCCM could regulate the Cd concentration in lettuce shoot by promoting microbial biodiversity of keystone modules in soil-root continuum and rhizosphere bacterial functions. These findings suggest that nano-biochar compost associations can be a superior strategy for enhancing microbial functions, maintaining soil health, and ensuring crop production safety in the Cd-contaminated soil compared to the mix of bulk-biochar and compost.

Evaluating the associations between intelligence quotient and multi-tissue proteome from the brain, CSF and plasma.

Intelligence quotient is a vital index to evaluate the ability of an individual to think rationally, learn from experience and deal with the environment effectively. However, limited efforts have been paid to explore the potential associations of intelligence quotient traits with the tissue proteins from the brain, CSF and plasma. The information of protein quantitative trait loci was collected from a recently released genome-wide association study conducted on quantification data of proteins from the tissues including the brain, CSF and plasma. Using the individual-level genotypic data from the UK Biobank cohort, we calculated the polygenic risk scores for each protein based on the protein quantitative trait locus data sets above. Then, Pearson correlation analysis was applied to evaluate the relationships between intelligence quotient traits (including 120 330 subjects for 'fluid intelligence score' and 38 949 subjects for 'maximum digits remembered correctly') and polygenic risk scores of each protein in the brain (17 protein polygenic risk scores), CSF (116 protein polygenic risk scores) and plasma (59 protein polygenic risk scores). The Bonferroni corrected P-value threshold was P < 1.30 × 10-4 (0.05/384). Finally, Mendelian randomization analysis was conducted to test the causal relationships between 'fluid intelligence score' and pre-specific proteins from correlation analysis results. Pearson correlation analysis identified significant association signals between the protein of macrophage-stimulating protein and fluid intelligence in brain and CSF tissues (P brain = 1.21 × 10-8, P CSF = 1.10 × 10-7), as well as between B-cell lymphoma 6 protein and fluid intelligence in CSF (P CSF = 1.23 × 10-4). Other proteins showed close-to-significant associations with the trait of 'fluid intelligence score', such as plasma protease C1 inhibitor (P CSF = 4.19 × 10-4, P plasma = 6.97 × 10-4), and with the trait of 'maximum digits remembered correctly', such as tenascin (P plasma = 3.42 × 10-4). Additionally, Mendelian randomization analysis results suggested that macrophage-stimulating protein (Mendelian randomization-Egger: ß = 0.54, P = 1.64 × 10-61 in the brain; ß = 0.09, P = 1.60 × 10-12 in CSF) had causal effects on fluid intelligence score. We observed functional relevance of specific tissue proteins to intelligence quotient and identified several candidate proteins, such as macrophage-stimulating protein. This study provided a novel insight to the relationship between tissue proteins and intelligence quotient traits.

A TrmBL2-like transcription factor mediates the growth phase-dependent expression of halolysin SptA in a concentration-dependent manner in Natrinema gari J7-2.

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a non-specific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cis-regulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. IMPORTANCE: Extracellular proteases play important roles in nutrient metabolism, processing of functional proteins, and antagonism of haloarchaea, but no transcription factor involved in regulating the expression of haloaechaeal extracellular protease has been reported yet. Here we report that a TrmBL2-like transcription factor (NgTrmBL2) mediates the growth phase-dependent expression of an extracellular protease, halolysin SptA, of haloarchaeon Natrinema gari J7-2. In contrast to its hyperthermophilic archaeal homologs, which are generally considered to be global transcription repressors, NgTrmBL2 functions as a positive regulator for sptA expression. This study provides new clues about the transcriptional regulation mechanism of extracellular protease in haloarchaea and the functional diversity of archaeal TrmBL2.

Body shape from birth to adulthood is associated with skeletal development: A Mendelian randomization study.

BACKGROUND: Observational studies have shown that childhood obesity is associated with adult bone health but yield inconsistent results. We aimed to explore the potential causal association between body shape and skeletal development. METHODS: We used two-sample Mendelian randomization (MR) to estimate causal relationships between body shape from birth to adulthood and skeletal phenotypes, with exposures including placental weight, birth weight, childhood obesity, BMI, lean mass, fat mass, waist circumference, and hip circumference. Independent genetic instruments associated with the exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding large-scale genome-wide association studies. The inverse-variance weighted analysis was chosen as the primary method, and complementary MR analyses included the weighted median, MR-Egger, weighted mode, and simple mode. RESULTS: The MR analysis shows strong evidence that childhood (ß = -1.29 × 10-3, P = 8.61 × 10-5) and adulthood BMI (ß = -1.28 × 10-3, P = 1.45 × 10-10) were associated with humerus length. Tibiofemoral angle was negatively associated with childhood BMI (ß = -3.60 × 10-1, P = 3.00 × 10-5) and adolescent BMI (ß = -3.62 × 10-1, P = 2.68 × 10-3). In addition, genetically predicted levels of appendicular lean mass (ß = 1.16 × 10-3, P = 1.49 × 10-13), whole body fat mass (ß = 1.66 × 10-3, P = 1.35 × 10-9), waist circumference (ß = 1.72 × 10-3, P = 6.93 × 10-8) and hip circumference (ß =1.28 × 10-3, P = 4.34 × 10-6) were all associated with tibia length. However, we found no causal association between placental weight, birth weight and bone length/width. CONCLUSIONS: This large-scale MR analysis explores changes in growth patterns in the length/width of major bone sites, highlighting the important role of childhood body shape in bone development and providing insights into factors that may drive bone maturation.

Comprehensive pan-cancer analysis reveals that C5orf34 regulates the proliferation and mortality of lung cancer.

The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive investigations of this gene are lacking. This study aims to elucidate the functional attributes and underlying mechanisms of C5orf34 in cancer. To evaluate its clinical predictive value, we conducted an analysis of the pan-cancerous expression, clinical data, mutation, and methylation data of C5orf34. Additionally, we investigated the correlation between C5orf34 and tumor mutant load (TMB), immune cell infiltration, and microsatellite instability (MSI) through relevant analyses. Furthermore, immunohistochemical (IHC) staining was employed to validate clinical samples, while knockdown and overexpression experiments and transcriptome RNA sequencing were utilized to examine the impact of C5orf34 on LUAD cells. According to our study, C5orf34 exhibits high expression levels in the majority of malignant tumors. The upregulation of C5orf34 is governed by DNA copy number alterations and methylation patterns, and it is closely associated with patients' survival prognosis and immune characteristics, thereby holding significant clinical implications. Furthermore, IHC staining analysis, cellular experiments, and transcriptome RNA sequencing have provided evidence supporting the role of C5orf34 in modulating the cell cycle to promote LUAD proliferation, migration, and invasion. This highlights its potential as a promising therapeutic target. The findings of this investigation suggest that C5orf34 may serve as a valuable biomarker for various tumor types and represent a potential target for immunotherapy, particularly in relation to the proliferation, migration, and apoptosis of LUAD cells.

Multimodal smart systems reprogramme macrophages and remove urate to treat gouty arthritis.

Gouty arthritis is a chronic and progressive disease characterized by high urate levels in the joints and by an inflammatory immune microenvironment. Clinical data indicate that urate reduction therapy or anti-inflammatory therapy alone often fails to deliver satisfactory outcomes. Here we have developed a smart biomimetic nanosystem featuring a 'shell' composed of a fusion membrane derived from M2 macrophages and exosomes, which encapsulates liposomes loaded with a combination of uricase, platinum-in-hyaluronan/polydopamine nanozyme and resveratrol. The nanosystem targets inflamed joints and promotes the accumulation of anti-inflammatory macrophages locally, while the uricase and the nanozyme reduce the levels of urate within the joints. Additionally, site-directed near-infrared irradiation provides localized mild thermotherapy through the action of platinum and polydopamine, initiating heat-induced tissue repair. Combined use of these components synergistically enhances overall outcomes, resulting in faster recovery of the damaged joint tissue.

Blood-Derived Extracellular Vesicles as a Promising Liquid Biopsy Diagnostic Tool for Early Cancer Detection.

Cancer poses a significant public health challenge worldwide, and timely screening has the potential to mitigate cancer progression and reduce mortality rates. Currently, early identification of most tumors relies on imaging techniques and tissue biopsies. However, the use of low-cost, highly sensitive, non-invasive detection methods for early cancer screening has become more attractive. Extracellular Vesicles (EVs) released by all living cells contain distinctive biological components, such as nucleic acids, proteins, and lipids. These vesicles play crucial roles in the tumor microenvironment and intercellular communication during tumor progression, rendering liquid biopsy a particularly suitable method for diagnosis. Nevertheless, challenges related to purification methods and validation of efficacy currently hinder its widespread clinical implementation. These limitations underscore the importance of refining isolation techniques and conducting comprehensive investigations on EVs. This study seeks to evaluate the potential of liquid biopsy utilizing blood-derived EVs as a practical, cost-effective, and secure approach for early cancer detection.