Adipose tissue is increasingly recognized as a highly heterogeneous secretory organ, and the extracellular vesicle-associated microRNAs (EV-miRNAs) it releases can act as peripheral molecular signals involved in long-distance regulation. Current evidence indicates that adipose-derived EV-miRNAs exhibit pronounced adipose depot- and cell-of-origin specificity, and that their composition can be dynamically altered by metabolic state. Following biogenesis and selective sorting, these miRNAs can be transported through the circulation within EVs and, under certain conditions, gain access to the central nervous system (CNS). Functional studies have shown that adipose-derived EV-miRNAs primarily act on neurons and, in some pathological models, modulate microglial function, thereby contributing to the regulation of hypothalamic energy homeostasis, learning and memory, emotional and stress-related responses, and neuroimmune processes. Obesity further remodels the adipose-derived EV-miRNA repertoire, enhancing pathological miRNA signals while concomitantly reducing certain homeostatic miRNA signals, thereby altering their regulatory effects on the central nervous system. This review systematically summarizes the tissue and cellular origins, biogenesis and selective sorting, circulatory transport and central delivery of adipose-derived EV-miRNAs, as well as their regulatory effects across multiple dimensions of brain function. Collectively, adipose-derived EV-miRNAs constitute an important molecular signaling layer through which adipose tissue states influence brain function; however, their source-specific profiles under physiological conditions, mechanisms of brain region- and cell-specific targeting, and causal roles and translational potential in human disease remain to be further elucidated.

Diabetic kidney disease (DKD) develops through maladaptive communication among glomerular, tubular, vascular and immune cells, but current clinical markers capture accumulated injury more readily than active molecular processes. Extracellular RNAs (exRNAs), including microRNAs, long noncoding RNAs, circular RNAs and messenger RNAs, are released in extracellular vesicles (EVs) or associated with ribonucleoproteins and lipoproteins. These carriers protect RNA against degradation and convey regulatory signals between cells, producing measurable molecular traces in urine and blood. In DKD models, exRNA pathways have been linked to podocyte loss, endothelial dysfunction, mesangial expansion, tubular stress, inflammation and fibrosis. Urinary EV-associated microRNAs have the most developed evidence from patient studies, with several varying alongside albuminuria or estimated glomerular filtration rate. Most of these studies are small and cross-sectional. Their findings are strongly affected by biofluid collection, EV enrichment, RNA normalization, treatment exposure and disease definition. Therapeutic studies remain preclinical, and effects of a nominated RNA must be separated from those of its carrier and co-packaged cargo. We critically assess biomarker and therapeutic evidence in relation to exRNA biology and renal cell-state transitions. The proposed staged translational framework addresses analytical validity, biological provenance, prospective clinical utility and scalable manufacturing. exRNA is therefore best viewed not as a single biomarker class, but as a platform whose value will depend on resolving cellular origin, context and causality.

Aim: Our previous studies identified three extracellular vesicle derived microRNAs (miR-92a-1-5p, miR-375 and miR-148a-3p) potentially associated with prostate cancer (PCa), particularly in advanced stages such as bone-metastatic PCa. This study aimed to evaluate their clinical diagnostic utility as a panel derived from plasma extracellular vesicles. Methods: A total of 49 treatment-naive participants, including 21 with benign prostatic hyperplasia (BPH), 15 with localized PCa, and 13 with bone-metastatic PCa, were enrolled. Plasma extracellular vesicles were isolated, and absolute quantification of the three miRNAs was performed using digital polymerase chain reaction (PCR). Their individual and combined diagnostic performance for distinguishing PCa from BPH and identifying bone metastasis was assessed. Results: Among the three miRNAs, miR-92a-1-5p and miR-375 showed a statistically significant difference in expression between PCa and BPH. The combined three-miRNA panel achieved an improved area under the curve (AUC) of 0.736, representing an enhancement over single markers and outperforming serum prostate-specific antigen (PSA) (AUC = 0.682) in this cohort. The panel yielded an AUC of 0.766 for detecting bone-metastatic PCa versus BPH, but showed limited ability to discriminate localized from metastatic disease. Conclusion: These preliminary findings suggest that the plasma extracellular vesicle-derived three-miRNA panel has auxiliary diagnostic value for differentiating prostate cancer from benign prostatic hyperplasia, and may serve as a supplementary tool to serum PSA.