Exosomal miR-221-3p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Asthma Progression by Targeting FGF2 and Inhibiting the ERK1/2 Signaling Pathway.

Exosomes derived from human bone marrow mesenchymal stem cells (BMSCs) play potential protective roles in asthma. However, the underlying mechanisms remain not fully elucidated. Herein, exosomes were isolated from BMSCs, and the morphology, particle size, and exosome marker proteins were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot, respectively. Then airway smooth muscle cells (ASMCs) were treated with transforming growth factor-ß1 (TGF-ß1) to construct a proliferation model and then incubated with BMSCs-derived exosomes. We found that exosome incubation increased miR-221-3p expression and inhibited proliferation, migration, and the levels of extracellular matrix (ECM) proteins including fibronectin and collagen III. Moreover, FGF2 was identified as a target gene of miR-221-3p. FGF2 overexpression reversed the inhibitory effects of exosomal miR-221-3p on ASMC progression. Besides, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) is inhibited by exosomal miR-221-3p, which was reversed by FGF2 overexpression. And ERK1/2 signaling activator reversed the effects of exosomal miR-221-3p on ASMC progression. Additionally, an ovalbumin (OVA)-induced asthmatic mice model was established, and exosome treatment alleviated airway hyper-responsiveness (AHR), histopathological damage, and ECM deposition in asthmatic mice. Taken together, our findings indicated that exosomal miR-221-3p derived from BMSCs inhibited FGF2 expression and the ERK1/2 signaling, thus attenuating proliferation, migration, and ECM deposition in ASMCs and alleviating asthma progression in OVA-induced asthmatic mice. Our findings may provide a novel therapeutic strategy for asthma.

Enhanced Adsorption of p-Arsanilic Acid from Water by Amine-Modified UiO-67 as Examined Using Extended X-ray Absorption Fine Structure, X-ray Photoelectron Spectroscopy, and Density Functional Theory Calculations.

p-Arsanilic acid ( p-ASA) is an emerging organoarsenic pollutant comprising both inorganic and organic moieties. For the efficient removal of p-ASA, adsorbents with high adsorption affinity are urgently needed. Herein, amine-modified UiO-67 (UiO-67-NH2) metal-organic frameworks (MOFs) were synthesized, and their adsorption affinities toward p-ASA were 2 times higher than that of the pristine UiO-67. Extended X-ray absorption fine structure (EXAFS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation results revealed adsorption through a combination of As-O-Zr coordination, hydrogen bonding, and π-π stacking, among which As-O-Zr coordination was the dominant force. Amine groups played a significant role in enhancing the adsorption affinity through strengthening the As-O-Zr coordination and π-π stacking, as well as forming new adsorption sites via hydrogen bonding. UiO-67-NH2s could remove p-ASA at low concentrations (<5 mg L-1) in simulated natural and wastewaters to an arsenic level lower than that of the drinking water standard of World Health Organization (WHO) and the surface water standard of China, respectively. This work provided an emerging and promising method to increase the adsorption affinity of MOFs toward pollutants containing both organic and inorganic moieties, via modifying functional groups based on the pollutant structure to achieve synergistic adsorption effect.