Network pharmacology-and molecular docking-based investigation of Danggui blood-supplementing decoction in ischaemic stroke.

Danggui blood-supplementing decoction (DBsD) is an herbal preparation treating several diseases including stroke. The present study sought to investigate the potential mechanism of DBsD in ischaemic stroke (IS) using network pharmacology, molecular docking, and cell experiment. Based on the protein-protein (PPI) network analysis, MAPK1 (0.51, 12), KNG1 (0.57, 28), and TNF (0.64, 39) were found with relatively good performance in degree and closeness centrality. The functional enrichment analysis revealed that DBsD contributed to IS-related biological processes, molecule function, and presynaptic/postsynaptic cellular components. Pathway enrichment indicated that DBsD might protect IS by modulating multi-signalling pathways including the sphingolipid signalling pathway. Molecular docking verified the stigmasterol-KNG1, bifendate-TNF, and formononetin-MAPK1 pairs. Cell experiments confirmed the involvement of KNG1 and sphingolipid signalling pathway in hippocampal neuronal cell apoptosis. This study showed that DBsD can protect neuronal cell injury after IS through multiple components, multiple targets, and multiple pathways.

Azilsartan attenuates lipopolysaccharide-induced acute lung injury via the Nrf2/HO-1 signaling pathway.

Acute lung injury (ALI) is a severe complication of sepsis and hemorrhagic shock with high morbidity. In the present study, the protective effect of Azilsartan on lipopolysaccharide (LPS)-induced ALI in mice was investigated to explore the potential therapeutic property of Azilsartan for the treatment of ALI. LPS was used to induce an ALI model in mice. Hematoxylin-eosin (HE) staining sections were then evaluated for the pathological state of lung tissues. Bronchoalveolar lavage fluid (BALF) protein concentration, wet/dry weight ratios of lung tissues, and pulmonary myeloperoxidase (MPO) activity were detected to determine the degree of pulmonary injury. The number of total cells, macrophages, and neutrophils in BALF were counted using a hemocytometer to illustrate the inflammatory cell infiltration. The lung function was monitored using a spirometer. The concentrations of interleukin-1ß (IL-1ß), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were determined using enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated by the superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) concentrations in the lung tissue. The expressions of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined using Western blot analysis. Azilsartan therapy alleviated LPS-induced lung tissue damage, increased BALF protein concentration, lung wet to dry weight ratio, MPO activity, and macrophage and neutrophils infiltration. Also, Azilsartan ameliorated the production of inflammatory factors (IL-1ß, MCP-1, and IL-8). Azilsartan ameliorated LPS-impaired lung SOD activity, the GSH concentration, and the MDA concentration. Mechanistically, Azilsartan activated the LPS-impaired Nrf2/HO-1 signaling pathway. Azilsartan therapy attenuates LPS-induced ALI via the Nrf2/HO-1 signaling pathway.

Safe angle scope for posterior atlanto-occipital transarticular screw fixation.

OBJECTIVE: To study the technical parameters related to, and explore the clinical significance of, posterior atlanto-occipital transarticular screw fixation. METHODS: Posterior implantation of Kirschner wires via the atlanto-occipital joint was performed on 20 dry bone specimens with complete atlanto-occipital joints. The angle of the Kirschner wire was measured on a postimplantation x-ray. Three-dimensional computed tomographic reconstruction of the atlanto-occipital joint of 30 healthy adults was performed to measure the simulative safety range for screw placement in posterior atlanto-occipital transarticular screw fixation. The procedure was then conducted on 12 fresh cadaver occipitocervical specimens. X-rays and 3-dimensional computed tomographic reconstruction were performed postsurgery to verify exact screw positioning. RESULTS: The ideal angles for screw placement were cephalocaudal angle in the sagittal plane of 53.3 +/- 3.4 degrees, mediolateral angle in the coronal plane of 20.0 +/- 2.6 degrees, a maximum allowable cephalocaudal angle of 74.6 +/- 2.8 degrees (67.9-80.5 degrees), a minimum allowable cephalocaudal angle of 24.9 +/- 1.9 degrees (22.1-29.4 degrees), a maximum allowable mediolateral angle of 40.5 +/- 2.9 degrees (31.1-49.4 degrees), and a minimum allowable mediolateral angle of 0.7 +/- 1.6 degrees (-4.1-5.9 degrees). Surgery simulation in the fresh cadaver specimens indicated that this safe scope is reliable. CONCLUSION: There is a safe scope for the angle of the screw placement in posterior atlanto-occipital transarticular screw fixation. Posterior transarticular screw fixation can be safely performed for occipitocervical fusion fixation when utilizing careful screw placement.