Strictosamide alleviates acute lung injury via regulating T helper 17 cells, regulatory T cells, and gut microbiota.

BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.

Research progress on expansive soil cracks under changing environment.

Engineering problems shunned previously rise to the surface gradually with the activities of reforming the natural world in depth, the problem of expansive soil crack under the changing environment becoming a control factor of expansive soil slope stability. The problem of expansive soil crack has gradually become a research hotspot, elaborates the occurrence and development of cracks from the basic properties of expansive soil, and points out the role of controlling the crack of expansive soil strength. We summarize the existing research methods and results of expansive soil crack characteristics. Improving crack measurement and calculation method and researching the crack depth measurement, statistical analysis method, crack depth and surface feature relationship will be the future direction.

Expansive soil crack depth under cumulative damage.

The crack developing depth is a key problem to slope stability of the expansive soil and its project governance and the crack appears under the roles of dry-wet cycle and gradually develops. It is believed from the analysis that, because of its own cohesion, the expansive soil will have a certain amount of deformation under pulling stress but without cracks. The soil body will crack only when the deformation exceeds the ultimate tensile strain that causes cracks. And it is also believed that, due to the combined effect of various environmental factors, particularly changes of the internal water content, the inherent basic physical properties of expansive soil are weakened, and irreversible cumulative damages are eventually formed, resulting in the development of expansive soil cracks in depth. Starting from the perspective of volumetric strain that is caused by water loss, considering the influences of water loss rate and dry-wet cycle on crack developing depth, the crack developing depth calculation model which considers the water loss rate and the cumulative damages is established. Both the proposal of water loss rate and the application of cumulative damage theory to the expansive soil crack development problems try to avoid difficulties in matrix suction measurement, which will surely play a good role in promoting and improving the research of unsaturated expansive soil.