Lycium barbarum polysaccharides ameliorate LPS-induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice.

In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNF-α, IL-1ß, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential anti-inflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. PRACTICAL APPLICATIONS: In recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)-induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity. In addition, by intraperitoneal injection of LPS to establish peritonitis mice models, LBP pretreatment was found to have significantly modified the behavioral score of mice, while decreasing the secretion of inflammatory factors and the damage to several organs. The present study provides a basis for further understanding the effects of LBP in acute inflammation.

MiR-129-5p Restrains Apatinib Resistance in Human Gastric Cancer Cells Via Downregulating HOXC10.

Background: Repeated administration of apatinib has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that miR-129-5p had a low expression in GC, and homeobox gene C10 (HOXC10), a carcinogenic gene, was highly expressed in GC, while the molecular mechanism of miR-129-5p involved in apatinib resistance in GC cells is still unclear. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-129-5p and HOXC10 in GC tissues or cell lines. The expression levels of associated proteins were detected by Western blot. Cell counting kit-8 (CCK-8), the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and flow cytometry assays were conducted to detect cell viability, proliferation, and apoptosis of MGC-803/AP and AGS/AP cells in vitro. The dual-luciferase reporter assay was used to verify the targeted relationship between miR-129-5p and HOXC10. The xenograft model was established to examine the effect of miR-129-5p in vivo, and the HOXC10 protein expression in tumor xenograft was assessed by immunohistochemistry. Results: MiR-129-5p had a low expression in GC tissues and apatinib-resistant cell lines, while HOXC10 was highly expressed. Meanwhile, overexpression of miR-129-5p and knockdown of HOXC10 could enhance the chemosensitivity of MGC-803/AP and AGS/AP cells. Dual-luciferase reporter assay confirmed miR-129-5p targeted HOXC10 and downregulated its expression level. MiR-129-5p inhibited proliferation and promoted apoptosis of MGC-803/AP and AGS/AP cells by downregulating HOXC10. The experiment in vivo also confirmed that miR-129-5p reduced apatinib resistance in GC cells by targetedly inhibiting HOXC10. HOXC10 was upregulated in GC tumor xenograft tissues. Conclusion: miR-129-5p restrains apatinib-resistant of GC cells by regulating HOXC10.