Introduction: Exosomes, nano-sized extracellular vesicles, are known to circulate through the blood stream to transfer molecular signals from tissue to tissue. Methods: To determine whether exosomes affect aging in animals, we primarily identified the changes in exosomal miRNA contents during the aging process. In exosomes from 12-month-old mice, mmu-miR-126-5p and mmu-miR-466c-5p levels were decreased and mmu-miR-184-3p and mmu-miR-200b-5p levels were increased significantly compared with those of 3-month-old mice. Their levels in exosomes were partially correlated with those in tissues: levels of only mmu-miR-126-5p and mmu-miR-466c-5p in lungs and/or liver were decreased, but those of mmu-miR-184-3p and mmu-miR-200b-5p in tissues did not coincide with those of exosomes. Results and discussion: In the aged tissues injected with young exosomes isolated from serum, mmu-miR-126b-5p levels were reversed in the lungs and liver. Expression changes in aging-associated molecules in young exosome-injected mice were obvious: p16Ink4A, MTOR, and IGF1R were significantly downregulated in the lungs and/or liver of old mice. In addition, telomerase-related genes such as Men1, Mre11a, Tep1, Terf2, Tert, and Tnks were significantly upregulated in the liver of old mice after injection of young exosomes. Conclusion: These results indicate that exosomes from young mice could reverse the expression pattern of aging-associated molecules in aged mice. Eventually, exosomes may be used as a novel approach for the treatment and diagnosis of aging animals.
Magnetic nanoparticle-conjugated polymeric micelles (MNP-PMs) consisting of poly(ethylene glycol)-poly(lactide) (PEG-PLA) and iron oxide nanoparticles were prepared and used as nanocarriers for combined hyperthermia and chemotherapy. Doxorubicin (DOX) was encapsulated in MNP-PMs, and an alternating magnetic field (AMF) resulted in an increase to temperature within a suitable range for inducing hyperthermia and a higher rate of drug release than observed without AMF. In vitro cytotoxicity and hyperthermia experiments were carried out using human lung adenocarcinoma A549 cells. When MNP-PMs encapsulated with an anticancer drug were used to treat A549 cells in combination with hyperthermia under AMF, 78% of the cells were killed by the double effects of heat and the drug, and the combination was more effective than either chemotherapy or hyperthermia treatment alone. Therefore, MNP-PMs encapsulated with an anticancer drug show potential for combined chemotherapy and hyperthermia.
Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI–TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker—detected via a liquid biopsy—for the noninvasive diagnosis of lung cancer.
1 January 2018 in Oxidative Medicine and Cellular Longevity
Cigarette smoke contains more than 4,500 chemicals; most of which are highly reactive free radicals, which induce proinflammatory and carcinogenic reactions. Numerous efforts have focused extensively on the role of cigarette smoking as a cause of many diseases. Extracellular vesicles and exosomes have recently received increasing interest for their diagnostic and therapeutic roles in many diseases. However, research done on the role of extracellular vesicles and exosomes on cigarette smoke‐induced chronic disease is still in its infancy. In this review, we summarize the recently addressed roles of extracellular vesicles and exosomes in the pathogenesis of cigarette smoke‐related diseases, such as chronic obstructive pulmonary disease, cardiovascular disease, lung cancer, and oral cancer. Moreover, their potential utilization and future prospects as diagnostic biomarkers for cigarette smoke‐related diseases are described.