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Abstract Background As an anticancer Chinese herbal medicine, the effective components and mechanism of Actinidia chinensis Planch (ACP, Tengligen) in the treatment of colon cancer are still unclear. In the present study, the integration of network pharmacology, molecular docking, and cell experiments was employed to study the effective mechanism of ACP against colon cancer. Methods The Venn diagram and STRING database were used to construct the protein–protein interaction network (PPI) of ACP-colon cancer, and further topological analysis was used to obtain the key target genes of ACP in colon cancer. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to visualize the related functions and pathways. Molecular docking between key targets and compounds was determined using software such as AutoDockTools. Finally, the effect of ACP on CT26 cells was observed in vitro. Results The study identified 40 ACP-colon key targets, including CASP3, CDK2, GSK3B, and PIK3R1. GO and KEGG enrichment analyses found that these genes were involved in 211 biological processes and 92 pathways, among which pathways in cancer, PI3K-Akt, p53, and cell cycle might be the main pathways of ACP against colon cancer. Molecular docking verified that the key components of ACP could stably bind to the corresponding targets. The experimental results showed that ACP could inhibit proliferation, induce apoptosis, and downregulate the phosphorylation of PIK3R1, Akt, and GSK3B in CT26 cells. Conclusion ACP is an anti-colon cancer herb with multiple components, and involvement of multiple target genes and signaling pathways. ACP can significantly inhibit proliferation and induce apoptosis of colon cancer cells, which may be closely related to the regulation of PI3K/AKT/GSK3B signal transduction.

Abstract Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial–mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs.

Context Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer’s disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear.Objective Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism.Materials and methods UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 μM), ATS (40 μM), UA (5 μM) + ATS (40 μM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected.Results The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 μM) + ATS (ED50: 40 μM) could protect H2O2-induced (IC50: 250 μM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1.Conclusions ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.

Abstract Background Glioblastoma (GBM) has a high incidence rate, invasive growth, and easy recurrence, and the current therapeutic effect is less than satisfying. Pyroptosis plays an important role in morbidity and progress of GBM. Meanwhile, the tumor microenvironment (TME) is involved in the progress and treatment tolerance of GBM. In the present study, we analyzed prognosis model, immunocyte infiltration characterization, and competing endogenous RNA (ceRNA) network of GBM on the basis of pyroptosis-related genes (PRGs). Methods The transcriptome and clinical data of 155 patients with GBM and 120 normal subjects were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Lasso (Least absolute shrinkage and selection operator) Cox expression analysis was used in predicting prognostic markers, and its predictive ability was tested using a nomogram. A prognostic risk score formula was constructed, and CIBERSORT, ssGSEA algorithm, Tumor IMmune Estimation Resource (TIMER), and TISIDB database were used in evaluating the immunocyte infiltration characterization and tumor immune response of differential risk samples. A ceRNA network was constructed with Starbase, mirtarbase, and lncbase, and the mechanism of this regulatory axis was explored using Gene Set Enrichment Analysis (GSEA). Results Five PRGs (CASP3, NLRP2, TP63, GZMB, and CASP9) were identified as the independent prognostic biomarkers of GBM. Prognostic risk score formula analysis showed that the low-risk group had obvious survival advantage compared with the high-risk group, and significant differences in immunocyte infiltration and immune related function score were found. In addition, a ceRNA network of messenger RNA (CASP3, TP63)–microRNA (hsa-miR-519c-5p)–long noncoding RNA (GABPB1-AS1) was established. GSEA analysis showed that the regulatory axis played a considerable role in the extracellular matrix (ECM) and immune inflammatory response. Conclusions Pyroptosis and TME-related independent prognostic markers were screened in this study, and a prognosis risk score formula was established for the first time according to the prognosis PRGs. TME immunocyte infiltration characterization and immune response were assessed using ssGSEA, CIBERSORT algorithm, TIMER, and TISIDB database. Besides a ceRNA network was built up. This study not only laid foundations for further exploring pyroptosis and TME in improving prognosis of GBM, but also provided a new idea for more effective guidance on clinical immunotherapy to patients and developing new immunotherapeutic drugs.

BackgroundSolanum nigrum L. (SNL) (Longkui) is a Chinese herb that can be used to treat colon cancer. The present study explored the components and mechanisms of SNL in treating colon cancer by using network pharmacology and molecular docking.MethodsThe components of SNL were collected from the TCMSP, ETCM, HERB, and NPASS databases. Meanwhile, the target proteins of these ingredients were collected/predicted by the TCMSP, SEA, SwissTargetPrediction, and the STITCH databases colon cancer-related target genes were identified from TCGA and GTEx databases. The interaction networks were established via Cytoscape 3.7.2. Gene Ontology and KEGG pathways were enriched by using the David 6.8 online tool. Finally, the binding of key components and targets was verified by molecular docking, and the cellular thermal shift assay (CETSA) was used to detect the efficiency of apigenin and kaempferol binding to the AURKB protein in CT26 cells.ResultsA total of 37 SNL components, 796 SNL targets, 5,356 colon cancer genes, and 241 shared targets of SNL and colon cancer were identified. A total of 43 key targets were obtained through topology analysis. These key targets are involved in multiple biological processes, such as signal transduction and response to drug and protein phosphorylation. At the same time, 104 signaling pathways, such as pathways in cancer, human cytomegalovirus infection, and PI3K-Akt signaling pathway, are also involved. The binding of the four key components (i.e., quercetin, apigenin, kaempferol, and luteolin) and the key targets was verified by molecular docking. The CETSA results showed that apigenin and kaempferol were able to bind to the AURKB protein to exert anti-CRC effects.ConclusionsQuercetin, apigenin, kaempferol, and luteolin are the main components of SNL in treating colon cancer. SNL regulates multiple bioprocesses via signaling pathways, such as pathways in cancer, PI3K-Akt, and cell cycle signaling pathways.

Background: Teng-Long-Bu-Zhong-Tang (TLBZT) is a traditional Chinese herbal medicine used to treat colorectal cancer (CRC). In the present study, we observed the anti-cancer effects of TLBZT on human RKO CRC. Materials and Methods: Mice were subcutaneously transplanted with RKO cells, divided into control, 5-Fu-administered, TLBZT-administered, and TLBZT and 5-Fu combination-administered groups, and treated with 5-Fluorouracil (5-Fu) and/or TLBZT. Apoptosis was detected by TdT-mediated dUTP nick-end labeling assay. The activity of caspase-3,-8, and-9 was detected using specific commercial kits. Cell senescence was assessed using senescence β-galactosidase staining. Protein expression was evaluated by immunohistochemistry. Results: TLBZT inhibited RKO CRC tumor growth, enhanced the anti-cancer effects of 5-Fu, induced apoptosis, and activated caspase-3,-8, and-9. TLBZT induced cell senescence accompanied by the downregulation of cyclin E1 and cyclin-dependent kinase 2 expressions. TLBZT also inhibited angiogenesis and the expression of hypoxia-inducible factor 1 subunit alpha and vascular endothelial growth factor-A. Conclusions: TLBZT inhibited RKO CRC tumor growth and enhanced the anti-cancer effects of 5-Fu, and it could be associated with apoptosis and cell senescence induction, and angiogenesis inhibition.

Abstract Background Ursolic acid (UA) is an anti-cancer herbal compound. In the present study, we observed the effects of UA on anchorage-dependent and -independent growth of human colorectal cancer (CRC) RKO cells. Methods RKO cells were cultured in conventional and detached condition and treated with UA. Cell viability was evaluated by CCK-8 assay. Cell cycle was analyzed by flow cytometry. Apoptosis was identified by Hoechst 33258 staining and flow cytometry analysis. Activities of caspases were measured by commercial kits. Reactive oxygen species (ROS) was recognized by DCFH-DA fluorescent staining. Anoikis was identified by EthD-1 fluorescent staining and flow cytometry analysis. Expression and phosphorylation of proteins were analyzed by western blot. Results UA inhibited RKO cell viability in both a dose- and time-dependent manner. UA arrested the cell cycle at the G0/G1 phase, and induced caspase-dependent apoptosis. UA inhibited Bcl-2 expression and increased Bax expression. In addition, UA up-regulated the level of ROS that contributed to UA activated caspase-3, − 8 and − 9, and induced apoptosis. Furthermore, UA inhibited cell growth in a detached condition and induced anoikis in RKO cells that was accompanied by dampened phosphorylation of FAK, PI3K and AKT. UA also inhibited epithelial-mesenchymal transition (EMT) as indicated by the down-regulation of N-Cad expression and up-regulation of E-Cad expression. Conclusions UA induced caspase-dependent apoptosis, and FAK/PI3K/AKT singling and EMT related anoikis in RKO cells. UA was an effective anti-cancer compound against both anchorage-dependent and -independent growth of RKO cells.

Momentum collimation in a high-intensity rapid cycling synchrotron (RCS) is a very important issue. Based on the two-stage collimation principle, a combined momentum collimation method is proposed and studied in detail here. The method makes use of the combination of secondary collimators in both the longitudinal and transverse planes. The primary collimator is placed at a high-dispersion location of an arc, and the longitudinal and transverse secondary collimators are in the same arc and in the adjacent downstream dispersion-free long straight section, respectively. The particles with positive momentum deviations will be scattered and degraded by a carbon scraper and then collected mainly by the transverse collimators, whereas the particles with negative momentum deviations will be scattered by a tantalum scraper and mainly collected by the longitudinal secondary collimators. This is to benefit from the different effects of protons passing through a high atomic number material and a low atomic number material, as the former produces relatively more scattering than the latter for the same energy loss. The studies also reveal that momentum collimation is strongly dependent on the transverse beam correlation that comes from the injection painting. The relevant requirements on the lattice design are also discussed, especially for compact rings. The multiparticle simulations using both TURTLE and ORBIT codes are presented to show the physical images of the collimation method, which was carried out with the input of the RCS of China Spallation Neutron Source.

Context: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. Objective: Network pharmacology was used to explore the mechanism of UAþATS in treating AD, and cell experiments were used to verify the mechanism. Materials and methods: UAþATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UAþATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2þ solvent pre-treatment), UA (5 lM), ATS (40 lM), UA (5 lM) þ ATS (40 lM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. Results: The key targets of UAþATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5lM) þ ATS (ED50: 40lM) could protect H2O2-induced (IC50: 250lM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. Conclusions: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling. [ABSTRACT FROM AUTHOR]

Abstract Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p

Some factors influencing the production of cream fluoride glass are discussed. Based on operational data and design experiences for the electric melting furnace with a production capacity of 5 t/d cream fluoride glass, characteristics of this furnace are introduced. [ABSTRACT FROM AUTHOR]