A p53-TLR3 axis ameliorates pulmonary hypertension by inducing BMPR2 via IRF3

Pulmonary arterial hypertension (PAH) features pathogenic and abnormal endothelial cells (ECs), and one potential origin is clonal selection. We studied the role of p53 and toll-like receptor 3 (TLR3) in clonal expansion and pulmonary hypertension (PH) via regulation of bone morphogenetic protein (BMPR2) signaling. ECs of PAH patients had reduced p53 expression. EC-specific p53 knockout exaggerated PH, and clonal expansion reduced p53 and TLR3 expression in rat lung CD117+ ECs. Reduced p53 degradation (Nutlin 3a) abolished clonal EC expansion, induced TLR3 and BMPR2, and ameliorated PH. Polyinosinic/polycytidylic acid [Poly(I:C)] increased BMPR2 signaling in ECs via enhanced binding of interferon regulatory factor-3 (IRF3) to the BMPR2 promoter and reduced PH in p53−/− mice but not in mice with impaired TLR3 downstream signaling. Our data show that a p53/TLR3/IRF3 axis regulates BMPR2 expression and signaling in ECs. This link can be exploited for therapy of PH

Structure and properties of biodegradable PLLA/ZnO composite membrane produced via electrospinning

These days, composite materials based on polymers and inorganic nanoparticles (NPs) are widely used in optoelectronics and biomedicine. In this work, composite membranes of polylactic acid and ZnO NPs containing 5–40 wt.% of the latter NPs were produced by means of electrospinning. For the first time, polymer material loaded with up to 40 wt.% of ZnO NPs (produced via laser ablation in air and having non-modified surface) was used to prepare fiber-based composite membranes. The morphology, phase composition, mechanical, spectral and antibacterial properties of the membranes were tested by a set of analytical techniques including SEM, XRD, FTIR, UV-vis, and photoluminescence spectroscopy. Antibacterial activity of the materials was evaluated following standard procedures (ISO 20743:2013) and using S. aureus and E. coli bacteria. It is shown that incorporation of 5–10 wt.% of NPs led to improved mechanical properties of the composite membranes, while further increase of ZnO content up to 20 wt.% and above resulted in their noticeable deterioration. At the same time, the antibacterial properties of ZnO-rich membranes were more pronounced, which is explained by a larger number of surface-exposed ZnO NPs, in addition to those embedded into the bulk of fiber material. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Environmental drivers of Sphagnum growth in peatlands across the Holarctic region

Contains fulltext : 231306.pdf (Publisher’s version ) (Open Access