Icariin Regulates EMT and Stem Cell-Like Character in Breast Cancer through Modulating lncRNA NEAT1/TGFß/SMAD2 Signaling Pathway.

Metastases and drug resistance are the major risk factors associated with breast cancer (BC), which is the most common type of tumor affecting females. Icariin (ICA) is a traditional Chinese medicine compound that possesses significant anticancer properties. Long non-coding RNAs (lncRNAs) are involved in a wide variety of biological and pathological processes and have been shown to modulate the effectiveness of certain drugs in cancer. The purpose of this study was to examine the potential effect of ICA on epithelial mesenchymal transition (EMT) and stemness articulation in BC cells, as well as the possible relationship between its inhibitory action on EMT and stemness with the NEAT1/transforming growth factor ß (TGFß)/SMAD2 pathway. The effect of ICA on the proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony assays), EMT (Western blotting, immunofluorescence, and wound healing), and stemness (mammosphere formation assays, Western blotting) of BC cells were examined. According to the findings, ICA suppressed the proliferation, EMT, and stem cell-like in MDA-MB-231 cells, and exerted its inhibitory impact by downregulating the TGFß/SMAD2 signaling pathway. ICA could significantly downregulate the expression of lncRNA NEAT1, and silencing NEAT1 enhanced the effect of ICA in suppressing EMT and expression of different stem cell markers. In addition, silencing NEAT1 was found to attenuate the TGFß/SMAD2 signaling pathway, thereby improving the inhibitory impact of ICA on stemness and EMT in BC cells. In conclusion, ICA can potentially inhibit the metastasis of BC via affecting the NEAT1/TGFß/SMAD2 pathway, which provides a theoretical foundation for understanding the mechanisms involved in potential application of ICA for BC therapy.

[Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway].

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

[Effect of fengshining capsule on reactive oxygen species-mediated T cell activation and apoptosis of synovium].

OBJECTIVE: To study the effect of intracellular reactive oxygen species (ROS) levels on T cell activation and apoptosis of synovial cells in collagen induced arthritis (CIA) rats, and to explore the mechanism of Fengshining Capsule (FSN) in the treatment of rheumatoid arthritis (RA). METHODS: Sixty rats were randomly divided into the normal control group, the CIA model group, the Tripterygium Poly-glycoside Tablet (TPT) group, the low dose FSN group (at the daily dose of 0.33 g/kg), the middle dose FSN group (at the daily dose of 0.66 g/kg), and the high dose FSN group (at the daily dose of 1.32 g/kg), 10 in each group. T lymphocyte subsets were detected by flow cytometry. The content of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in plasma of rats were detected by ELISA. Its expression of hydroxyl radicals was detected by ultraviolet spectrophotometry. Caspase-3 and Caspase-9 protein expressions were measured by Western blot. RESULTS: Compared with the CIA model group, the levels of ROS were elevated in each dose FSN group (P < 0.01). The level of CD4+ / CD8 was significantly reduced in the middle dose FSN group (P < 0.01). The content of IFN-gamma was obviously lowered in each dose FSN group (P < 0.01), while that of IL-4 was obviously elevated in the high dose FSN group (P < 0.01). Meanwhile, the expression of Caspase-9 and Caspase-3 significantly increased in each dose FSN group (P < 0.05). Besides, the average gray scale of Caspase-9 was significantly higher in the low and middle FSN groups than in the TPT group (P < 0.05, P < 0.01). CONCLUSION: The mechanism of FSN for regulating the immune hyperfunction and inhibiting the proliferation of synovial cells in CIA rats might be associated with up-regulating in vivo ROS levels.