A Mixture of Baicalein, Wogonin, and Oroxylin-A Inhibits EMT in the A549 Cell Line via the PI3K/AKT-TWIST1-Glycolysis Pathway.

Non-small cell lung cancer (NSCLC) is a worldwide disease with a high morbidity and mortality rate, which is most derived from its metastasis. Some studies show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cell migration and invasion, leading to NSCLC metastasis. Total flavonoid aglycones extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds [baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)], the reconstructed TFAE (reTFAE) inhibited the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of the PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through the glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.

Activation of Müller cells occurs during retinal degeneration in RCS rats.

Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local 'glial seal' in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration.

[How to deal with cerebral palsy in 21st century--a new epoch in clinic treatment].

The aims of this paper were to define (1) criteria of cerebral palsy; (2) classification of cerebral palsy; (3) etiology, neuroimaging, and epidemiology of cerebral palsy; (4) different kinds of treatments of cerebral palsy. Data were drawn from an international survey of PUBMED (1994-2014) and CNKI (1994-2014). An expert panel used a consensus building technique. The10-point Jadad scale was used to assess the quality of the trials based on the following items, including allocation sequence generation, randomization concealment, methods of blinding, and descriptions of withdrawals and dropouts. Our clinical experience was also summarized. Below is a summary. (1) Further work is warranted to reach agreement for the classification of cerebral palsy. (2) A worldwide prevalence of 1.5-4.0 per 1 000 live births, with an average lifetime cost of 1 million dollars per person in the United States, while it is 1.8-6.0 per 1000 live births in China. (3) Comparison of clinical efficacy of different treatments. In this review, the current advances in different kind of treatments of brain injury are discussed with specific relevance to cerebral palsy.