Bufotalin attenuates pulmonary fibrosis via inhibiting Akt/GSK-3ß/ß-catenin signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented ß-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-ß1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3ß Ser9 (p-GSK-3ß S9), thereby reactivating GSK-3ß. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3ß/ß-catenin axis downstream of TGF-ß1. Thus, BT could be a potential option to be further explored in IPF treatment.

Migrasome: a new functional extracellular vesicle.

Migrasome is a novel cellular organelle produced during cell migration, and its biogenesis depends on the migration process. It is generated in a variety of cells such as immune cells, metastatic tumor cells, other special functional cells like podocytes and cells in developing organisms. It plays important roles in various fields especially in the information exchange between cells. The discovery of migrasome, as an important supplement to the extracellular vesicle system, provides new mechanisms and targets for comprehending various biological or pathological processes. In this article, we will review the discovery, structure, distribution, detection, biogenesis, and removal of migrasomes and mainly focus on summarizing its biological functions in cell-to-cell communication, homeostatic maintenance, embryonic development and multiple diseases. This review also creates prospects for the possible research directions and clinical applications of migrasomes in the future.

TLR4 Agonist MPLA Ameliorates Heavy-Ion Radiation Damage via Regulating DNA Damage Repair and Apoptosis.

Heavy-ion radiation received during radiotherapy as well as the heavy-ion radiation received during space flight are equally considered harmful. Our previous study showed that TLR4 low toxic agonist, monophosphoryl lipid A (MPLA), alleviated radiation injury resulting from exposure to low-LET radiation. However, the role and mechanism of MPLA in heavy-ion-radiation injury are unclear. This study aimed to investigate the role of MPLA on radiation damage. Our data showed that MPLA treatment alleviated the heavy-ion-induced damage to microstructure and the spleen and testis indexes. The number of karyocytes in the bone marrow from the MPLA-treated group was higher than that in the irradiated group. Meanwhile, western blotting analysis of intestine proteins showed that pro-apoptotic proteins (cleaved-caspase3 and Bax) were downregulated while anti-apoptotic proteins (Bcl-2) were upregulated in the MPLA-treated group. Our in vitro study demonstrated that MPLA significantly improved cell proliferation and inhibited cell apoptosis after irradiation. Moreover, immunofluorescence staining and quantification of nucleic γ-H2AX and 53BP1 foci also suggested that MPLA significantly attenuated cellular DNA damage repair. Collectively, the above evidence supports the potential ability of MPLA to protect against heavy-ion-radiation injury by inhibiting apoptosis and alleviating DNA damage in vivo and vitro, which could be a promising medical countermeasure for the prevention of heavy-ion-radiation injury.

Experimental Study on Single Corner Cold Bending Mechanical Response of Laminated of PVB Interlayer Tempered Glass Panes and the Coupling Effect with Load.

The cold bending method is a type of curved glass curtain wall construction method that has been used in practical engineering for a short time. It has the advantages of simple operation, high efficiency and low cost. However, the mechanical response and properties of glass panes caused by cold bending have not been solved effectively. To study the mechanical response and the properties of cold formed laminated tempered glass panes after applying with a wind load, cold bending and load tests of 9 laminated tempered glass panes were conducted by the orthogonal experimental design method. The effects of cold bending curvature, glass pane thickness and interlayer thickness were considered. In this paper, the response law of cold bending stress to the curvature and the relationship among the influencing factors were analyzed. The variation process of stress, the deflection of cold-formed glass panes under uniform load and the characteristics affected by cold-formed stress and deformation were studied. The results show that the cold bending stress is distributed in a saddle shape, and the curvature has the greatest influence on the cold bending stress, followed by the thickness of the glass panes. The influence of the interlayer thickness is small. The maximum stress appears near the corner of the short side direction adjacent to the cold bending corner. The cold bending stress increases linearly with increasing cold bending curvature. The cold bending stress and deformation have little effect on the change process of the later stage load effect.

Study on the mechanical response of anticlastic cold bending insulating glass and its coupling effect with uniform load.

Cold bending is a characteristic of significance for the beautiful curved glass curtain walls, because it affects them in terms of energy-efficiency and cost-efficiency. The increasing engineering projects call for more special studies on the mechanical properties of cold-bent glass panels, especially when the walls are built by insulating glass that is currently widely used while its relevant research is very scarce. This paper is devoted to studying the mechanical properties of anticlastic cold-bent insulating glass while taking different factors into consideration, including glass thickness, cold-bent torsion rate and cavity thickness. 9 pieces of insulating glass were manufactured for anticlastic cold-bending test and their coupled effect with identical load is also studied, and numerical finite element analysis sessions were carried out to simulate the experimental results for each one of them. Further, we analyzed the stress distribution performance of the sample pieces under cold bending and a uniform load, followed by discussions about stress transfer controls in glass plates. The results showed that the cold-bent control stress is on the surface with direct loads from cold bending and close to the cold-bent corner on the short edge, and it is transferred from the parts around the corner to the center when the uniform load plays a leading role in generating stress. This transfer could occur under a relatively small load with a small cold-bent torsion rate. A higher cold-bent torsion rate in cold bending contributed mostly to greater center stress in the glass, and as the glass thickness grows, stress and deflection at the plate center would significantly drop. However, the effect of cavity thickness on the anticlastic mechanical response of insulating glass was found to be trivial.