RESUMEN
With the continuous deepening of Artificial Neural Network (ANN) research, ANN model structure and function are improving towards diversification and intelligence. However, the model is more evaluated from the pros and cons of the problem-solving results and the lack of evaluation from the biomimetic aspect of imitating neural networks is not inclusive enough. Hence, a new ANN models evaluation strategy is proposed from the perspective of bionics in response to this problem in the paper. Firstly, four classical neural network models are illustrated: Back Propagation (BP) network, Deep Belief Network (DBN), LeNet5 network, and olfactory bionic model (KIII model), and the neuron transmission mode and equation, network structure, and weight updating principle of the models are analyzed qualitatively. The analysis results show that the KIII model comes closer to the actual biological nervous system compared with other models, and the LeNet5 network simulates the nervous system in depth. Secondly, evaluation indexes of ANN are constructed from the perspective of bionics in this paper: small-world, synchronous, and chaotic characteristics. Finally, the network model is quantitatively analyzed by evaluation indexes from the perspective of bionics. The experimental results show that the DBN network, LeNet5 network, and BP network have synchronous characteristics. And the DBN network and LeNet5 network have certain chaotic characteristics, but there is still a certain distance between the three classical neural networks and actual biological neural networks. The KIII model has certain small-world characteristics in structure, and its network also exhibits synchronization characteristics and chaotic characteristics. Compared with the DBN network, LeNet5 network, and the BP network, the KIII model is closer to the real biological neural network.
RESUMEN
Berberine (BBR), a natural alkaloid derived from Coptis, has anticancer activity. Some researchers have found that it could restrain epithelial-mesenchymal transition (EMT) of melanoma, neuroblastoma, and other tumor cells. However, it is unclear whether BBR can reverse EMT in hepatocellular carcinoma (HCC) and gastric carcinoma (GC). In our study, BBR inhibited the migration and invasion of HepG2, MGC803, and SGC7901 cells in a dose-dependent manner. Transcription sequencing assays showed that Vimentin, MMP, and Smad3 were downregulated, but Smad2, Smad6, TAB2, ZO-1, and claudin 7 were upregulated when treated with BBR. GO Enrichment analysis of KEGG pathway showed that BBR significantly inhibited TGF-ß/Smad at 12 h, then, PI3K/Akt and Wnt/ß-catenin signaling pathways at 24 h, which were closely related to the proliferation, migration, and EMT. The results of the transcriptome sequencing analysis were verified by Western Blot. It showed that the expression of epithelial marker E-cadherin and ZO-1 remarkably augmented with BBR treatment, as well as declined mesenchymal markers, including N-cadherin and Vimentin, decreased transcription factor Snail and Slug. The effects of BBR were similar to those of the PI3K inhibitor LY294002 and TGF-ß receptor inhibitor SB431542. Furthermore, ß-catenin and phosphorylation of AKT, Smad2, and Smad3 were changed dose-dependently by BBR treatment, which upregulated p-Smad2 and downregulated the others. Combined with LY or SB, respectively, BBR could enhance the effects of the two inhibitors. Simultaneously, IGF-1 and TGF-ß, which is the activator of PI3K/AKT and TGF-ß/Smad, respectively, could reverse the anti-EMT effect of BBR. The Molecular Docking results showed BBR had a high affinity with the TGF-ß receptor I (TGFßR1), and the binding energy was -7.5 kcal/mol, which is better than the original ligand of TGFßR1. Although the affinity of BBR with TGF-ß receptor II (TGFßR2) was lower than the original ligand of TGFßR2, the more considerable negative binding energy (-8.54 kcal/mol) was obtained. BBR upregulated p-Smad2, which was different from other reports, indicating that the function of Smad2 was relatively complex. Combination BBR with SB could enhance the effect of the inhibitor on EMT, and the results indicated that BBR binding to TGFßR was not competitive with SB to TGFßR since different binding amino acid sites. Our experiments demonstrated BBR increased p-Smad2 and decreased p-Smad3 by binding to TGFßR1 and TGßFR2 inhibiting TGF-ß/Smad, then, PI3K/AKT and other signaling pathways to restrain EMT, metastasis, and invasion in tumor cells. The effect of BBR was similar on the three tumor cells.