Aging Us
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Old age is a known risk factor for mortality in acute respiratory distress syndrome (ARDS)/acute lung injury. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, while aging MSCs have reduced capacity. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) are able to mimic MSCs in alleviating acute lung injury. ⋯ In addition, the internalization of aging MSC-EVs by macrophages was significantly lower compared with that of young MSC-EVs. Furthermore, aging and young MSC-EVs differed in levels of several miRNAs relating macrophage polarization. In conclusion, aging and young MSC-EVs have differential effects in alleviating acute lung injury and macrophage polarization, which may be associated with internalization of EVs and their miRNA content.
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Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of gastric cancer; however, their mechanisms of action remain largely unknown. The aim of this study was to identify lncRNAs involved in the tumorigenesis of gastric cancer and to investigate the signaling pathways they affect. Using microarray and RT-qPCR analyses, candidate lncRNAs were screened in paired gastric cancer tissues. ⋯ Using RNA pull-down and mass-spectrometry analyses we found and verified a direct and novel interaction between MIR4435-2HG and desmoplakin (DSP), the most abundant desmosomal protein. Overexpression and knockdown experiments revealed opposing roles for DSP and MIR4435-2HG, unmasking a cascade through which MIR4435-2HG binds to and inhibits DSP, leading to activation of WNT/β-catenin signaling and epithelial-mesenchymal transition in gastric cancer cells. We propose that the MIR4435-2HG/DSP/WNT axis serves as a critical effector of carcinogenesis and progression of gastric cancer, and could be exploited therapeutically to improve patients' outcomes.