[Safety toxicological evaluation of Wen Radix Codonopsis].

OBJECTIVE: To evaluate the toxicological safety of Wen Radix Codonopsis. METHODS: According to the national standards of food safety(GB 15193.3-2014, GB 15193.4-2014, GB 15193.5-2014, GB 15193.8-2014, GB 15193.13-2015), acute oral toxicity test, three genetic toxicity tests(including bacterial recovery mutation test, mammalian erythrocyte micronucleus test and mouse spermatocyte chromosome aberration test) and subchronic toxicity test were conducted in this study. RESULTS: The LD_(50) of Wen Radix Codonopsis to KM mouse was more than 38.72 g/kg, which was actually non-toxic according to the acute toxicity grading standard of mouse. The results of three genetic toxicity tests were negative and no obvious genotoxicity was observed. 90-day oral toxicity test showed that the overall growth condition of the rats in each group was good, and the test index result of each test group showed no statistical significance compared with the negative control group, and all of them were within the normal range in our laboratory. No abnormality was observed in gross anatomy, and no histopathological changes and specific lesions associated with the test substances were found. CONCLUSION: No obvious acute oral toxicity, genetic toxicity and subchronic toxicity were observed in Wen Radix Codonopsis under the present conditions.

Research on the Multimodal Digital Teaching Quality Data Evaluation Model Based on Fuzzy BP Neural Network.

We propose in this paper a fuzzy BP neural network model and DDAE-SVR deep neural network model to analyze multimodal digital teaching, establish a multimodal digital teaching quality data evaluation model based on a fuzzy BP neural network, and optimize the initial weights and thresholds of BP neural network by using adaptive variation genetic algorithm. Since the BP neural network is highly dependent on the initial weights and points, the improved genetic algorithm is used to optimize the initial weights and thresholds of the BP neural network, reduce the time for the BP neural network to find the importance and points that satisfy the training termination conditions, and improve the prediction accuracy and convergence speed of the neural network on the teaching quality evaluation results. The entropy value method, a data-based objectivity evaluation method, is introduced as the guidance mechanism of the BP neural network. The a priori guidance sample is obtained by the entropy method. Then, the adaptive variational genetic algorithm is used to optimize the BP neural network model to learn the a priori sample knowledge and establish the evaluation model, which reduces the subjectivity of the BP neural network learning sample. To better reflect and compare the effects of the two neural network evaluation models, BP and GA-BP, the sample data were continued to be input into the original GA and BSA to obtain the evaluation results and errors; then, the evaluation results of the two evaluation models, BP and GA-BP, were compared with the evaluation results of the two algorithms, GA and BSA. It was found that the GA-BP neural network evaluation model has higher accuracy and can be used for multimodal digital teaching quality evaluation, providing a more feasible solution.

Advances in Understanding the LncRNA-Mediated Regulation of the Hippo Pathway in Cancer.

Long noncoding RNAs (lncRNAs) are a class of RNA molecules that are longer than 200 nucleotides and cannot encode proteins. Over the past decade, lncRNAs have been defined as regulatory elements of multiple biological processes, and their aberrant expression contributes to the development and progression of various malignancies. Recent studies have shown that lncRNAs are involved in key cancer-related signaling pathways, including the Hippo signaling pathway, which plays a prominent role in controlling organ size and tissue homeostasis by regulating cell proliferation, apoptosis, and differentiation. However, dysregulation of this pathway is associated with pathological conditions, especially cancer. Accumulating evidence has revealed that lncRNAs can modulate the Hippo signaling pathway in cancer. In this review, we elaborate on the role of the Hippo signaling pathway and the advances in the understanding of its lncRNA-mediated regulation in cancer. This review provides additional insight into carcinogenesis and will be of great clinical value for developing novel early detection and treatment strategies for this deadly disease.

Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells.

Long non-coding RNAs (lncRNAs) can play significant regulatory roles in cells that affect the development and acquired drug resistance of lung cancer. Herein, we report that lncRNA linc00665 is significantly upregulated in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. linc00665 affects the sensitivity of NSCLC cells to the chemotherapy drug cisplatin (DDP), making it a potential target for the treatment of NSCLC. Functional experiments showed that linc00665 enhanced the proliferation and migration of NSCLC cells in vivo and in vitro, and knocking down linc00665 could enhance the drug sensitivity of NSCLC cells to DDP. Further work revealed that linc00665 could recruit enhancer of zeste homolog 2 (EZH2) to the promoter region of cyclin-dependent kinase inhibitor 1C (CDKN1C) to inhibit its transcription and thus carry out its tumorigenic role. In conclusion, our study elucidated the carcinogenic role of the linc00665-EZH2-CDKN1C axis in NSCLC tumors and its ability to influence the sensitivity of these tumors to DDP. These results suggest that linc00665 may be a potential diagnostic marker and therapeutic target in NSCLC, and they also provide a new direction for the development of clinical reversal methods for acquired drug resistance in patients with NSCLC.

Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has greatly affected clinical outcomes in non-small cell lung cancer (NSCLC) patients. The long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to NSCLC gefitinib resistance remain poorly understood. In this study, by analyzing the differentially expressed lncRNAs in gefitinib-resistant cells and gefitinib-sensitive cells in the National Institute of Health GEO dataset, we found that lncRNA CASC9 expression was upregulated, and this was also verified in resistant tissues. Gain and loss of function studies showed that CASC9 inhibition restored gefitinib sensitivity both in vitro and in vivo, whereas CASC9 overexpression promoted gefitinib resistance. Mechanistically, CASC9 repressed the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2, thereby increasing the resistance to gefitinib. Furthermore, ectopic expression of DUSP1 increased gefitinib sensitivity by inactivating the ERK pathway. Our results highlight the essential role of CASC9 in gefitinib resistance, suggesting that the CASC9/EZH2/DUSP1 axis might be a novel target for overcoming EGFR-TKI resistance in NSCLC.

Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based on Subcellular Proteomics and Bioinformatical Analysis.

TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.

The Impact of MMP-2 and Its Specific Inhibitor TIMP-2 Expression on the WHO Grade and Prognosis of Gliomas in Chinese Population: a Meta-Analysis.

So far, the prognostic value of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) expressions in patients with gliomas has been widely reported, especially in China. But, the results were inconsistent. Thus, we conducted a meta-analysis to determine the correlation of MMP-2 and TIMP-2 expressions with the prognosis of patients with gliomas. Identical search strategies were used to search relevant literature in electronic databases updated to May 1, 2015, and odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots and Egger's tests were conducted for the evaluation of publication bias, and heterogeneity and sensitivity were also analyzed. Finally, a total of 25 studies involving 1572 patients were included in the meta-analysis. Coincidentally, all these studies were conducted in Chinese population. It was found that MMP-2 expression was significantly associated with high-WHO grade gliomas (n = 24, OR = 6.54, CI = 4.98-8.60; I 2 = 0 %, P = 0.911) and poor overall survival (OS), while it did not correlate to age (n = 2, OR = 0.78, CI = 0.35-1.74; I 2 = 0 %, P = 0.621) and gender (n = 2, OR = 1.15, CI = 0.51-2.62; I 2 = 0 %, P = 0.995). Moreover, the results of the pooled analysis indicated that there was no association between TIMP-2 expression and the WHO grade of gliomas (n = 7, OR = 1.02, 95 % CI = 0.68-1.54; I 2 = 71.4 %, P = 0.002), but the ratio of MMP-2 and TIMP-2 (MMP-2/TIMP-2) rose with the increase of the WHO grade of gliomas. In conclusion, there was no correlation between TIMP-2 expression and the WHO grade of gliomas, while MMP-2 expression was potently associated with high-WHO grade of gliomas.