Exosomes are cell-derived vesicles and are abundant in biological fluids; they contain RNA molecules which may serve as potential diagnostic biomarkers in 'precision medicine'. To promote the ...clinical application of exosomal RNA (exoRNA), many isolation methods must be compared and validated. Exosomes in cell culture medium (CCM) and serum may be isolated using ultracentrifugation (UC), ExoQuick or Total Exosome Isolation Reagent (TEI), and exoRNA may be extracted using TRIzol-LS, SeraMir, Total Exosome RNA Isolation (TER), HiPure Liquid RNA/miRNA kit (HLR), miRNeasy or exoRNeasy. ExoRNA was assessed using NanoDrop, Bioanalyzer 2100, quantitative polymerase chain reaction and high-throughput sequencing. UC showed the lowest recovery of particles, but the highest protein purity for exosome isolation. For isolation of exoRNA, we found that combinations of the TEI and TER methods resulted in high extraction efficiency and purity of small RNA obtained using CCM. High yield and a narrow size distribution pattern of small RNA were shown in exoRNA isolated by exoRNeasy from serum. In RNA profile analysis, the small RNA constituent ratio, miRNA content and amount varied as a result of methodological differences. This study showed that different methods may introduce variations in the concentration, purity and size of exosomes and exoRNA. Herein we discuss the advantages and disadvantages of each method and their application to different materials, therefore providing a reference according to research design.
Inspired by the swimming of natural microorganisms, synthetic micro‐/nanomachines, which convert energy into movement, are able to mimic the function of these amazing natural systems and help ...humanity by completing environmental and biological tasks. While offering autonomous propulsion, conventional micro‐/nanomachines usually rely on the decomposition of external chemical fuels (e.g., H2O2), which greatly hinders their applications in biologically relevant media. Recent developments have resulted in various micro‐/nanomotors that can be powered by biocompatible fuels. Fuel‐free synthetic micro‐/nanomotors, which can move without external chemical fuels, represent another attractive solution for practical applications owing to their biocompatibility and sustainability. Here, recent developments on fuel‐free micro‐/nanomotors (powered by various external stimuli such as light, magnetic, electric, or ultrasonic fields) are summarized, ranging from fabrication to propulsion mechanisms. The applications of these fuel‐free micro‐/nanomotors are also discussed, including nanopatterning, targeted drug/gene delivery, cell manipulation, and precision nanosurgery. With continuous innovation, future autonomous, intelligent and multifunctional fuel‐free micro‐/nanomachines are expected to have a profound impact upon diverse biomedical applications, providing unlimited opportunities beyond one's imagination.
Fuel‐free synthetic micro‐/nanomachines powered by external stimuli are able to swim efficiently in biologically relevant environments. Tremendous progress made in the past decade to develop different synthesis strategies for designing and fabricating fuel‐free micro‐/nanomotors with different functionalities is reviewed. These artificial nanomachines can achieve predetermined tasks in biomedical applications.
Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 ...(PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion. Mechanistically, cisplatin induces PFKFB3 acetylation at lysine 472 (K472), which impairs activity of the nuclear localization signal (NLS) and accumulates PFKFB3 in the cytoplasm. Cytoplasmic accumulation of PFKFB3 facilitates its phosphorylation by AMPK, leading to PFKFB3 activation and enhanced glycolysis. Inhibition of PFKFB3 sensitizes tumor to cisplatin treatment in a xenograft model. Our findings reveal a mechanism for cells to stimulate glycolysis to protect from DNA damage and potentially suggest a therapeutic strategy to sensitize tumor cells to genotoxic agents by targeting PFKFB3.
The bioinspired micropatterns exhibit outstanding capacity in controlling and patterning microdroplets, which have offered new functionalities and possibilities towards a wide variety of emerging ...biological and biomedical applications. By taking the advantages of the microdroplet anchoring ability, enrichment ability, and the accessibility of such bioinspired micropatterns, the selected topic mainly focuses on the important aspects related to (super)wettable surfaces and their emerging sensing applications (DNA, miRNA, proteins,
etc.
) by combining them with multiple signal output approaches (fluorescence, colorimetric, SERS, electrochemical,
etc.
). In the end, we also provide a personal perspective on the future development, and address the remaining challenges in the commercialization of (super)wettable micropatterns towards biosensing.
The bioinspired micropatterns exhibit outstanding capacity in controlling and patterning microdroplets, which have offered new functionalities and possibilities towards a wide variety of emerging biological and biomedical applications.
The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. ...Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.
Synopsis
Aerobic exercise leads to skeletal muscle remodelling. This study reveals that dietary succinate is sufficient to elicit muscle remodelling and increased endurance in sedentary mice.
Dietary succinate increases endurance exercise ability in mice.
Dietary succinate induces skeletal muscle fiber transition from fast‐twitch to slow‐twitch.
SUNCR1 signaling pathway is required for the succinate induced skeletal muscle remodeling.
Aerobic exercise leads to skeletal muscle remodelling. This study reveals that dietary succinate is sufficient to elicit muscle remodelling and increased endurance in sedentary mice.
Natural antioxidants are widely distributed in food and medicinal plants. These natural antioxidants, especially polyphenols and carotenoids, exhibit a wide range of biological effects, including ...anti-inflammatory, anti-aging, anti-atherosclerosis and anticancer. The effective extraction and proper assessment of antioxidants from food and medicinal plants are crucial to explore the potential antioxidant sources and promote the application in functional foods, pharmaceuticals and food additives. The present paper provides comprehensive information on the green extraction technologies of natural antioxidants, assessment of antioxidant activity at chemical and cellular based levels and their main resources from food and medicinal plants.
A nanodendritic gold/graphene-based biosensor that can perform fluorescence, SERS and electrochemical tri-modal miRNA detection in a single microdroplet has been developed. The biosensor was used to ...successfully perform tri-modal quantitative trace miRNA-375 detection, which enormously reduces false positive readings caused by interference and ambiguous signals, and has significant implications for use in precise physiological and pathological diagnosis.
Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought ...to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.
By combining a superwettable interface with a nanodendritic gold structure, we have fabricated a superwettable nanodendritic gold substrate for direct SERS detection of multiple concentrations of ...miRNAs. The nanodendritic gold substrate provides numerous hotspots for Raman signal enhancement, and the superwettable interface ensures the immobilization of droplets in superhydrophilic microwells, which hold great potentials for applications in disease diagnostics.
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