Search Results (1,045)

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management. Full article

Background: Vulvar cancer mainly affects postmenopausal women, but its incidence is rising among younger individuals due to persistent HPV infection. Validated diagnostic biomarkers remain lacking, though circulating exosomal microRNAs (exomiRs) have recently emerged as promising liquid biopsy tools across various cancers. Objective: The purpose of this study was to identify a panel of dysregulated plasma-derived extracellular vesicle (EV)-associated miRNAs, hereafter referred to as exosomal micro-RNAs, as liquid biopsy markers for the detection of vulvar cancer and for assessment of HPV-positivity. Methods: Five healthy donor (HD) and 10 vulvar cancer samples underwent Next-Generation Sequencing to screen for differentially expressed exomiRs. The seven most dysregulated and four stably expressed exomiRs were subsequently analyzed in 81 cancer and 60 HD samples by qRT-PCR. Differential expression was determined by the 2^−ΔΔCT method. Binary regression was used to construct an exomiR panel. HPV status was assessed using mass spectrometry. Results: Five single exomiRs showed a statistically significant dysregulation in cancer patients compared to healthy controls: miR-143-3p, miR-223-3p, miR-451a, miR-4516 and miR-151a-5p. The combination of six exomiRs resulted in a panel with superior diagnostic ability (p < 0.001; ROC-AUC = 0.805; 95% CI: 0.726–0.884) in distinguishing cancer patients from HDs. A model consisting of miR-223-3p, miR-143-3p and miR-451a could discriminate HPV-positive from -negative (p = 0.003; ROC-AUC = 0.939), and a model of miR-4516, miR-143-3p, miR-16-5p and miR-451a was predictive of lymph node positivity (p < 0.001, ROC-AUC = 0.786). Multivariate Cox regression showed that a model of downregulated miR-16-5p and upregulated miR-451a was significantly associated with poorer survival (p = 0.023). Conclusions: This study indicates the future potential of exomiRs as diagnostic and prognostic liquid biopsy markers for vulvar cancer. Full article

Prostate cancer (PCa) is the most common malignancy in men, characterized by significant genetic and epigenetic heterogeneity, which complicates both diagnosis and treatment processes. Epigenetic mechanisms—including DNA methylation, chromatin remodeling, and dysregulated non-coding RNAs (miRNAs, lncRNAs, circRNAs)—contribute to tumor initiation, progression, and therapy resistance, offering promising diagnostic and prognostic biomarker opportunities. Liquid biopsy technologies, such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, allow minimally invasive, real-time monitoring of tumor evolution and resistance mechanisms, complementing traditional biomarkers like PSA and supporting precision oncology approaches. Clinically implemented assays, including PCA3, ConfirmMDx, and ExoDx Prostate, along with emerging multi-analyte panels, enhance risk stratification, reduce unnecessary biopsies, and guide therapeutic decisions. Integration of epigenetic and liquid biopsy biomarkers into multimodal diagnostic pathways has the potential to support personalized management of prostate cancer; however, many still require further validation and optimization. Full article

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management. Full article

Neuroblastoma is a highly aggressive pediatric malignancy originating from neural crest progenitor cells, predominantly in the adrenal medulla. Amplification of the MYCN oncogene occurs in 20–30% of all neuroblastoma cases and approximately 50% of high-risk tumors, strongly correlating with poor prognosis, relapse, and multidrug resistance. MYCN-driven oncogenesis promotes tumor progression by suppressing apoptotic signaling and enhancing survival pathways, including autophagy—a key mechanism underlying resistance to chemotherapy and immunotherapy. This review examines current therapeutic strategies and resistance mechanisms in MYCN-amplified neuroblastoma, while introducing emerging approaches utilizing exosomes as precision drug delivery systems. Exosomes, nanoscale extracellular vesicles secreted by the tumor cells, exhibit natural tropism and can be engineered to selectively target neuroblastoma-specific biomarkers such as glypican-2 (GPC2), which is highly expressed in MYCN-amplified tumors. Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine—an FDA-approved autophagy inhibitor—to simultaneously inhibit autophagy and induce apoptotic signaling. This dual-targeted approach aims to overcome drug resistance, reduce off-target toxicity, and enhance therapeutic efficacy through exosome-mediated specificity. Furthermore, gut dysbiosis has emerged as a critical factor influencing tumor progression and diminishing treatment efficacy in MYCN-amplified neuroblastoma. We propose integrating microbiota-derived exosomes engineered to deliver anti-inflammatory microRNAs (miRNAs) to the gut mucosa, restoring eubiosis and potentiating systemic anti-tumor responses. Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients. Full article

Objectives: To systematically analyze the expression profiles of long non-coding RNAs (lncRNAs) in serum-derived exosomes from patients with age-related hearing loss (ARHL), and to further identify key regulatory lncRNAs involved in the pathogenesis and progression of ARHL. Methods: Peripheral blood samples were collected from patients with ARHL and age-matched normal-hearing controls. Serum was separated and exosomes were extracted. The exosomes were identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blot. Subsequently, total RNA was extracted from the purified exosomes for lncRNA transcriptome sequencing. Based on the sequencing results, we identified differentially expressed lncRNAs and mRNAs and conducted multi-dimensional functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database (Reactome), and Disease Ontology (DO). Finally, four key mRNAs (THAP2, ZNF225, MED12, and RNF141) and four differentially expressed lncRNAs (DE-lncRNAs), namely MSTRG.150961.7, ENSG00000273015, MSTRG.336598.1, and ENSG00000273493, were experimentally verified by quantitative real-time polymerase chain reaction (RT-qPCR) technology. Results: Exosomes were successfully isolated from serum and confirmed by particle size, morphological examination, and the expression of exosome-labeled proteins. A total of 2874 DE-lncRNAs were identified, among which 988 were downregulated and 1886 were upregulated. Similarly, 2132 DE-mRNAs were detected, among which 882 were downregulated and 1250 were upregulated. GO analysis revealed significant enrichment in biological processes such as “phospholipid binding”, “phosphatidylinositol binding”, “phosphatase binding”, “phosphatidylinositol bisphosphate binding”, “phosphatidylinositol-4,5-bisphosphate binding”, “phosphatidylinositol-3,5-bisphosphate phosphatase activity”. KEGG is significantly enriched in signaling pathways including “Wnt signaling pathway”, “Hippo signaling pathway”, “Cushing syndrome”, and “Nucleocytoplasmic transport”. The functional annotations of Reactome were significantly enriched in biomolecular pathways including “tRNA processing”, “Cellular response to heat stress”, “Extra-nuclear estrogen signaling”, “Metabolism of non-coding RNA”, and “CTNNB1 T41 mutants aren’t phosphorylated”. DO is significantly enriched in diseases or pathological conditions such as “hepatitis”, “bacterial infectious disease”, “cystic fibrosis”, and “vasculitis”. Conclusions:THAP2, ZNF225, MED12, and RNF141 may serve as potential candidate biomarker for ARHL. Additionally, lncRNA MSTRG.150961.7, lncRNA MSTRG.336598.1, and lncRNA ENSG00000273493 may play significant roles in the pathogenesis of this condition. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, with its asymptomatic progression highlighting the urgent need for early, minimally invasive biomarkers. Exosomes derived from the aqueous humor (AH) have emerged as promising candidates, as they carry proteins, nucleic acids, and lipids that reflect the physiological and pathological state of ocular tissues such as the trabecular meshwork and ciliary body. However, their low abundance, nanoscale size, and the limited volume of AH complicate detection and characterization. Conventional methods, including Western blotting, PCR or mass spectrometry, are labor-intensive, time-consuming, and often incompatible with microliter-scale samples. Electrochemical biosensors offer a highly sensitive, rapid, and low-volume alternative, enabling the detection of exosomal surface markers and internal cargos such as microRNAs, proteins, and lipids. Recent advances in nanomaterial-enhanced electrodes, microfluidic integration, enzyme- and nanozyme-mediated signal amplification, and ratiometric detection strategies have significantly improved sensitivity, selectivity, and multiplexing capabilities. While most studies focus on blood or serum, these platforms hold great potential for AH-derived exosome analysis, supporting early-stage glaucoma diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. Continued development of miniaturized, point-of-care electrochemical biosensors could facilitate clinically viable, noninvasive exosome-based diagnostics for glaucoma. Full article

Sudden cardiac death (SCD) remains a major challenge in forensic medicine, representing a leading cause of natural mortality and frequently occurring in individuals without antecedent symptoms. Although conventional autopsy and histology remain the cornerstones of investigation, up to 10–15% of cases are classified as “autopsy-negative sudden unexplained death,” underscoring the need for complementary diagnostic tools. In recent years, post-mortem biochemistry and molecular approaches have become essential to narrowing this gap. Classical protein markers of myocardial necrosis (cardiac troponins, CK-MB, H-FABP, GPBB) continue to play a fundamental role, though their interpretation is influenced by post-mortem interval and sampling site. Peptide biomarkers reflecting hemodynamic stress (BNP, NT-proBNP, copeptin, sST2) offer additional insight into cardiac dysfunction and ischemic burden, while inflammatory and immunohistochemical markers (CRP, IL-6, fibronectin, desmin, C5b-9, S100A1) assist in detecting early ischemia and myocarditis when routine histology is inconclusive. Beyond these traditional markers, molecular signatures—including cardiac-specific microRNAs, exosomal RNA, proteomic alterations, and metabolomic fingerprints—provide innovative perspectives on metabolic collapse and arrhythmic mechanisms. Molecular autopsy through next-generation sequencing has further expanded diagnostic capability by identifying pathogenic variants associated with channelopathies and cardiomyopathies, enabling both cause-of-death clarification and cascade screening in families. Emerging multi-omics and artificial intelligence frameworks promise to integrate these heterogeneous data into standardized and robust interpretive models. Pre- and post-analytical considerations, together with medico-legal implications ranging from malpractice evaluation to the management of genetic information, remain essential components of this evolving field. Overall, the incorporation of validated biomarkers into harmonized international protocols, increasingly supported by AI, represents the next frontier in forensic cardiology. Full article

Seasonal biomass-burning haze in Northern Thailand produces sharp fluctuations in ambient fine particulate matter (PM), posing heightened health risks, particularly for individuals with diabetes mellitus (DM). To identify PM-responsive biomarkers and assess whether metabolic status modifies these responses, we first performed small RNA sequencing in a discovery cohort using plasma samples collected during low- and high-PM periods. Thirteen circulating microRNAs (miRNAs) were differentially expressed, including reduced miR-542-3p and elevated miR-29a-3p, novelmiR-203, and novelmiR-754, with predicted targets enriched in immune and endoplasmic-reticulum stress pathways. These four miRNAs were quantified by RT-qPCR in a longitudinal cohort of adults with (n = 28) and without DM (n = 29) sampled at three PM-defined timepoints across one full haze cycle. In non-DM individuals, miR-542-3p decreased at peak exposure while miR-29a-3p and novelmiR-203 increased, with values returning toward baseline at re-exposure. DM participants showed altered baseline levels and attenuated or reversed seasonal changes. Plasma IL-8 rose markedly at peak PM in both groups, mirroring exosome concentration increases measured by NTA, indicating a transient systemic inflammatory response. In an independent clinical cohort, only miR-542-3p differed significantly between lung-cancer patients and healthy controls. These findings indicate that PM exposure reconfigures circulating miRNA, exosomal, and cytokine profiles, and that DM modifies these responses, highlighting miR-542-3p and miR-29a-3p as environmentally responsive and disease-relevant biomarker candidates. Full article

Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves sequential protein complexes (ESCRT-0, I, II, III) that recognize and sort ubiquitinated cargo, induce membrane budding, and facilitate vesicle scission. In contrast, the ESCRT-independent pathway relies on membrane lipids such as ceramide and proteins like tetraspanins (CD9, CD63, CD81) to promote vesicle formation without ESCRT machinery. Furthermore, post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, further serve as molecular switches, modulating the affinity of ESCRT complexes or cargo proteins for membrane domains and affecting ILV formation rates. In reproductive medicine, exosomes regulate oocyte maturation, embryo–endometrial crosstalk, placental development, and maternal–fetal communication. Altered exosomal signaling contributes to obstetric complications, including preeclampsia, gestational diabetes mellitus, and preterm birth, whereas distinct exosomal miRNA signatures serve as potential diagnostic biomarkers. In gynecology, dysregulated exosomes are implicated in endometriosis, polycystic ovary syndrome, premature ovarian insufficiency, and gynecological malignancies. In contrast, mesenchymal stem cell-derived exosomes show therapeutic promise in restoring ovarian function and enhancing fertility outcomes. The distinctive molecular profiles of circulating exosomes enable minimally invasive diagnosis, while their biocompatibility and ability to cross biological barriers position them as vehicles for targeted drug delivery. Characterization of accessible data provides non-invasive opportunities for disease monitoring. However, clinical translation faces challenges, including standardization of isolation protocols, establishment of reference ranges for biomarkers, and optimization of therapeutic dosing. This review summarizes exosome biogenesis, characterization methods, physiological functions, and clinical applications in obstetrics and gynecology, with an emphasis on their diagnostic and therapeutic potential. Future directions include large-scale biomarker validation studies, engineering approaches to enhance exosome targeting, and integration with precision medicine platforms to advance personalized reproductive healthcare. Full article

Extracellular vesicles (EVs), particularly exosomes, are key mediators of intercellular communication, transporting biomolecules such as nucleic acids, lipids, and proteins that influence immune and metabolic pathways. In adipose tissue (AT), adipocyte-derived EVs (AdEVs) play a crucial role in maintaining metabolic homeostasis and have been implicated in obesity-related dysfunction. Among their bioactive cargo, microRNAs regulate post-transcriptional gene expression and participate in immunometabolic regulation. This study aimed to determine whether miR-34a expression in serum and circulating EVs varies according to body fat percentage, to explore its potential utility as a non-invasive biomarker of AT dysfunction. A total of 142 adults (mean age 36 ± 11 years) were classified by body fat percentage (≥25% in men, ≥35% in women). Exosomes were isolated (Invitrogen^®) and characterized by cryo-TEM, and miR-34a expression was quantified by qRT-PCR. miR-34a expression correlated negatively with Total Cholesterol, Triglycerides, LDLc/HDLc, TG/HDLc, BMI, C3, CRP, fasting insulin, HOMA-IR, HOMA-B, Body adiposity, Chemerin, CCL2, AdipoQT, and AdipoQ-H, but positively with HDLc and QUICKI. Notably, LDLc, sdLDLc, sdLDLc/LDLc, TC/HDLc, and fasting glucose showed opposite correlation patterns between serum and exosomes. Overall, serum miR-34a levels were higher than in exosomes, suggesting its potential as a biomarker of metabolic dysfunction and insulin resistance. Full article

Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article

Cancer immunotherapy has transformed oncology, but lasting responses are still limited due to resistance mechanisms within the tumor microenvironment. MicroRNAs (miRNAs) have emerged as critical regulators of immune checkpoint pathways, antigen presentation, T-cell activity, and macrophage polarization. By modulating both tumor-intrinsic and immune cell–intrinsic processes, miRNAs influence the efficacy of immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapies. Additionally, circulating and exosomal miRNAs are being investigated as minimally invasive biomarkers to predict patient response and resistance to immunotherapy. Clinical trials of miRNA-based treatments, including mimics and inhibitors, have highlighted both the promise and challenges of translating these molecules into clinical use. Advances in delivery systems, RNA chemistry, and combinatorial strategies are paving the way for their integration into precision immuno-oncology. This review offers a comprehensive overview of the mechanistic, biomarker, and therapeutic roles of miRNAs in cancer immunotherapy, highlighting ongoing clinical progress and prospects. Full article

Liquid biopsy and multi-omic biomarker integration are transforming precision oncology in breast cancer, providing real-time, minimally invasive insights into tumor biology. By analyzing circulating tumor DNA, circulating tumor cells, exosomal non-coding RNAs, and proteomic or metabolomic profiles, clinicians can monitor clonal evolution, therapeutic response, and recurrence risk in real time. Recent advances in sequencing technologies, methylation profiling, and artificial intelligence–driven data integration have markedly improved diagnostic sensitivity and predictive accuracy. Multi-omic frameworks combining genomic, transcriptomic, and proteomic data enable early detection of resistance, molecular stratification, and identification of actionable targets, while machine learning models enhance outcome prediction and therapy optimization. Despite these advances, key challenges persist. Pre-analytical variability, lack of standardized protocols, and disparities in access continue to limit reproducibility and clinical adoption. High costs, incomplete regulatory validation, and the absence of definitive evidence for mortality reduction underscore the need for larger, prospective trials. Integrating multi-omic assays into clinical workflows will require robust bioinformatics pipelines, clinician-friendly reporting systems, and interdisciplinary collaboration among molecular scientists, data engineers, and oncologists. In the near future, liquid biopsy is expected to complement, not replace, traditional tissue analysis, serving as a cornerstone of adaptive cancer management. As sequencing becomes faster and more affordable, multi-omic and AI-driven analyses will allow earlier detection, more precise treatment adjustments, and continuous monitoring across the disease course. Ultimately, these innovations herald a shift toward real-time, data-driven oncology that personalizes breast cancer care and improves patient outcomes. Full article

Background/Objectives: Cervical cancer remains a significant global health burden, underscoring the imperative for refined diagnostic and prognostic methodologies. This study aimed to evaluate the potential of extracellular vesicles (EVs) as non-invasive biomarkers for cervical cancer, focusing on diagnosis and prognosis. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines to assess the diagnostic and prognostic accuracy of EV-based biomarkers. We searched PubMed, EMBASE, and Web of Science for relevant studies. Twelve articles met the inclusion criteria: eight related to diagnostic accuracy, three to prognosis, and one to both outcomes. Six studies met the criteria for meta-analysis. We used a random-effects model to synthesise diagnostic data, while prognostic data were synthesised narratively. Results: The meta-analysis yielded a pooled area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.80–0.92) for EVs in the diagnosis of cervical cancer, indicating high accuracy. The evaluated diagnostic biomarkers were primarily non-coding RNAs. For prognosis, data heterogeneity precluded quantitative synthesis; however, individual studies identified diverse EV-associated molecules correlated with recurrence and survival. GRADE assessment indicated a high risk of bias and heterogeneity across studies. Conclusions: Extracellular vesicles demonstrate robust promise as diagnostic biomarkers for cervical cancer; however, their prognostic utility remains inconclusive due to methodological and clinical heterogeneity. Future research must prioritise the standardisation of isolation protocols and the execution of large-scale, prospective studies to validate EV biomarkers for clinical application. Systematic Review Registration: PROSPERO, identifier: CRD420251014411. Full article