Mechanism of Shishiwei Wendan Decoction in the Prevention and Treatment of Lung Adenocarcinoma Using Network Pharmacology and Molecular Docking.

Objective: This study used network pharmacology and molecular docking technology to elucidate the mechanism of action of Shishiwei Wendan Decoction against lung adenocarcinoma. Methods: By using the world's largest TCM System Pharmacology Database and Analysis Technology Platform (TCMSP) system to conduct in-depth mining analysis and data collection of the main active components of the medicinal components in Shishiwei Wendan Decoction and using the human gene card database (GeneCards), Human Mendelian Inheritance Online System (OMIM), and Human Disease-Related Gene and Mutation Information Database (DisGeNET) to collect the pathogenic targets of lung adenocarcinoma and build a PPI network; for the core drug targets, use GO enrichment analysis and KEGG pathway analysis; use Cytoscape software to build relevant network maps; and use AutoDock to achieve molecular docking. Results: Shishiwei Wendan Decoction screened 144 active ingredients and 384 drug targets; 7680 lung adenocarcinoma disease targets were obtained, including 380 targets for Shishiwei Wendan Decoction in the treatment of lung adenocarcinoma. GO enrichment analysis demonstrated 2,299 downstream genes, and key target genes were closely related to nutrient levels, membrane rafts, and protein serine/threonine kinase activity; KEGG functional enrichment analysis yielded 179 related pathways, including tumor necrosis factor signaling pathway which is related to the target gene. Molecular docking showed that the core active ingredients and key targets could be well combined. Conclusion: Through the network pharmacology analysis and molecular docking experiments of Shishiwei Wendan Decoction against lung adenocarcinoma, it is found that Shishiwei Wendan Decoction has multidimensional effects on the treatment of lung adenocarcinoma, and it is the first Shiwei Wendan Decoction to treat lung adenocarcinoma. Decoction in the treatment of lung adenocarcinoma provides biointellectual support and the oretical support.

Cement Leakage in Vertebral Compression Fractures Between Unilateral and Bilateral Percutaneous Vertebral Augmentation: A Meta-Analysis.

AIM: Cement leakage remains a significant clinical problem associated with vertebroplasty and kyphoplasty procedures, with uncontrolled cement flow in the posterior direction causing leakage into the vertebral veins or spinal canal that leads to potentially serious clinical complications. This meta-analysis compared the incidences of cement leakage between unilateral and bilateral percutaneous vertebral augmentation (PVA) in the treatment of osteoporosis vertebral compression fractures. MATERIAL AND METHODS: Pertinent studies were identified by a search of the PubMed, Embase, and Web of Science databases up to December 2020. The risk ratio (RR) or weighted mean difference (WMD) was applied to combine the results, and a random-effects or a fixed-effects model was used to pool the results depending on the heterogeneity among studies. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: A total of 16 trials (including 9 RCTs and 7 cohort studies) met the inclusion criteria and were included in this meta-analysis. The incidences of cement leakage were similar between the bilateral PVA and unilateral PVA groups (RR = 0.80, 95%CI: 0.57, 1.11; P = 0.182) but unilateral PVA required less cement volume (WMD = -1.34 ml, 95%CI: -1.87, -0.81; P 0.001). Subgroup analysis revealed that the incidence of cement leakage was significantly lower in the unilateral PKP group than in the bilateral PKP group (RR = 0.65, 95%CI: 0.44, 0.97; P = 0.034). CONCLUSION: The incidences of cement leakage were similar between unilateral and bilateral PVA, but unilateral PVA required less cement. More large-scale studies are needed to verify our findings.

Release characteristics of enoxaparin sodium-loaded polymethylmethacrylate bone cement.

BACKGROUND: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. METHODS: In the experimental group, 40 g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. RESULTS: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952, and 2.513, respectively, from the six groups with various ES loading amount of 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. CONCLUSION: The prepared ES-PMMA bone cement has high application potential in orthopedic surgery. ES-PMMA bone cement shows good drug release characteristics. The released enoxaparin sodium has a local anti-coagulant effect within 24 h after application, but it will not be released for a long time, which is complementary to postoperative anti-coagulation therapy.

CCL28 promotes locomotor recovery after spinal cord injury via recruiting regulatory T cells.

BACKGROUND: Chemokines play a key role in post-traumatic inflammation and secondary injury after spinal cord injury (SCI). CCL28, the chemokine CC-chemokine ligand 28, is involved in the epithelial and mucosal immunity. However, whether CCL28 participates in the physiopathologic processes after SCI remains unclear. RESULTS: CCL28 is upregulated in the spinal cord after SCI. In addition, neutralizing antibodies against IL-1ß or TNF-α, or treatment of ML120B, a selective inhibitor of IKK-ß, remarkably decrease CCL28 upregulation, suggesting that CCL28 upregulation relies on NF-κB pathway activated by IL-1ß and TNF-α after SCI. Moreover, CD4+CD25+FOXP3+ regulatory T (Treg) cells that express CCR10, a receptor of CCL28, are enriched in the spinal cord after SCI. We further demonstrate that the spinal cord recruits Treg cells through CCL28-CCR10 axis, which in turn function to suppress immune response and promote locomotor recovery after SCI. In contrast, neutralizing CCL28 or CCR10 reduces Treg cell recruitment and delays locomotor recovery. METHODS: The neutralizing antibodies and recombinant CCL28 were injected intraspinally into the mice prior to SCI, which was established via hemitransection. RT-qPCR analysis was performed to determine transcript level, and Western blot analysis and ELISA assay were used to detect protein expression. Immune cells were analyzed by flow cytometry and visualized by immunofluorescence. The chemotaxis was assessed by in vitro transwell migration assay. The mouse locomotor activity was assessed via the Basso Mouse Scale (BMS) system. CONCLUSIONS: These results indicate that NF-κB pathway-regulated CCL28 production plays a protective role after SCI through recruiting CCR10-expressing and immunosuppressive Treg cells, and suggest that interfering CCL28-CCR10 axis might be of potential clinical benefit in improving SCI recovery.