Actinidia chinensis Planch.root extract downregulates the Wnt/β-catenin pathway to treat gastric cancer:a mechanism study based on network pharmacology

Background:Actinidia chinensis Planch.roots(AcRoots)have been applied as an anti-inflammatory and antitumor drug in the treatment of gastric cancer(GC).However,their mechanisms against GC cells remain unclear.To investigate the anticancer effect of AcRoots in GC and the possible underlying mechanism by using network pharmacology.Methods:Differentially expressed genes between gastric precancerous lesions and cancer were analyzed in Gene Expression Omnibus datasets,and these genes were overlapped with potential targets of AcRoots.Potential targets and pathways for AcRoots treatment of GC predicted by network pharmacology.Furthermore,we used the GC cell line HGC27 to explore the molecular mechanisms in the context of hub genes in apoptosis,invasion,metastasis,and epithelial to mesenchymal transition-promoting factors.Molecular docking between hub targets and active drug components was also performed.Results:Network pharmacological analysis suggested that the potential mechanism was related to the Wnt pathway and predicted nine hub genes.In in vitro studies,AcRoots significantly decreased HGC27 cell viability and promoted apoptosis by upregulating caspase3 and downregulating Bcl2.Moreover,it suppressed invasion and metastasis as well as the expression of epithelial to mesenchymal transition-related factors.In addition,AcRoots affected the phosphorylation level of GSK3β(Ser9)in the Wnt pathway to promote the degradation ofβ-catenin,resulting in the downregulation of the downstream target genes c-myc,cyclin D1 and snail.All the experimental results were consistent with the network pharmacology results.Conclusion:This study combined network pharmacology with in vitro experiments to provide valid evidence for the clinical promotion of AcRoots.

Anti-Helicobacter pylori activities of Chenopodium ambrosioides L. in vitro and in vivo

AIM: To investigate the bactericidal effects of Chenopodium ambrosioides L.(CAL) against Helicobacter pylori(H.pylori) both in vitro and in vivo.METHODS: For in vitro experiments, the inhibitory activity of CAL was tested using an agar dilution method; H.pylori strain NCTC11637 was incubated on Columbia blood agar plates containing serial concentrations of CAL.The minimal inhibitory concentration(MIC) was determined by the absence of H.pylori colonies on the agar plate.Time-kill curves were used to evaluate bactericidal activity; the average number of colonies was calculated at 0, 2, 8 and 24 h after liquid incubation with concentrations of CAL at 0.5, 1, and 2 × MIC.For in vivo experiments, H.pylori-infected mice were randomly divided into CAL, triple therapy(lansoprazole, metronidazole, and clarithromycin), blank control, or H.pylori control groups.The eradication ratios were determined by positive findings from rapid urease tests(RUTs) and by histopathology.RESULTS: In vitro, the MIC of CAL against H.pylori was 16 mg/L.The time-kill curves showed a stable and persistent decreasing tendency with increasing CAL concentration, and the intensity of the bactericidal effect was proportional to dose; the 1 and 2 × MIC completely inhibited the growth of H.pylori at 24 h.In vivo, the eradication ratios in the CAL group were60%(6/10) by RUT and 50%(5/10) by histopathology.Ratios in the triple therapy group were both 70%(7/10), and there was no difference between the CAL and triple therapy groups.Histopathologic evaluation revealed massive bacterial colonization on the surface of gastric mucosa and slight infiltration of mononuclear cells after inoculation with H.pylori, but no obvious inflammation or other pathologic changes in gastric mucosa of mice from CAL and triple therapy groups.CONCLUSION: CAL demonstrates effective bactericidal activity against H.pylori both in vitro and in vivo.

Squeeze casting of aluminum alloy A380: Microstructure and tensile behavior

A380 alloy with a relatively thick cross-section of 25 mm was squeeze cast using a hydraulic press with an applied pressure of 90 MPa. Microstructure and tensile properties of the squeeze cast A380 were characterized and evaluated in comparison with the die cast counterpart. Results show that the squeeze cast A380 possesses a porosity level much lower than the die cast alloy, which is disclosed by both optical microscopy and the density measurement technique. The results of tensile testing indicate the improved tensile properties, specifically ultimate tensile strength(UTS: 215.9 MPa) and elongation(Ef: 5.4%), for the squeeze cast samples over those of the conventional high-pressure die cast part(UTS: 173.7 MPa, Ef: 1.0%). The analysis of tensile behavior shows that the squeeze cast A380 exhibits a high tensile toughness(8.5 MJ·m-3) and resilience(179.3 k J·m-3) compared with the die cast alloy(toughness: 1.4 MJ·m-3, resilience: 140.6 k J·m-3), despite that, during the onset of plastic deformation, the strain-hardening rate of the die cast specimen is higher than that of the squeeze cast specimens. The microstructure analyzed by the scanning electron microscopy(SEM) shows that both the squeeze and die cast specimens contain the primary α-Al, Al2 Cu, Al5 Fe Si phase and the eutectic Si phase. But, the Al2 Cu phase present in the squeeze cast alloy is relatively large in size and quantity. The SEM fractography evidently reveals the ductile fracture features of the squeeze cast A380 alloy.

Effect of pouring and cooling temperatures on microstructures and mechanical properties of as-cast and T6 treated A356 alloy

The A356 castings were fabricated using a well-developed temperature controlled permanent mold.To improve the strength and hardness of cast A356,the microstructures and mechanical properties of as-cast and T6 heat treated A356 alloy with various mold and pouring temperatures were studied.The results reveal that the undercooling is closely related to the mold and pouring temperatures.As the mold/pouring temperature changed from 258°C/680°C and 270°C/680°C to 288°C/650°C,the in-situ undercooling is 12°C,17°C and 11°C,respectively.It is observed that the Si phase changes from long continuous flake to discontinuous globular-fibrous morphology after T6 heat treatment as the mold and pouring temperature is 270°C/680°C,and the T6 heat treated specimens exhibit better mechanical properties in comparison to those as-cast ones with an increase of 162%and 102%in yield strength and elongation,which are 34.6%and 190%higher than the ASTM B108-03 a standard,respectively.As a result,the tensile fracture morphology of the as-cast A356 alloy shows quasi-cleavage fracture and the T6 heat treated A356 alloy shows ductile fracture.

Analysis of the medication rules of the national patent compound for the treatment of functional dyspepsia

Objective:Based on data mining software,applying frequent itemsets,association rules,hierarchical clustering,complex networks and other data mining methods to analyze the usage and compatibility of traditional Chinese medicine(TCM)patent compound for functional dyspepsia.Method:Use the Chinese patent database to search the compound for the treatment of functional dyspepsia,exclude traditional Chinese medicine extracts,single drugs,combined use of Chinese and Western medicines,etc.,screen the patented compound of TCM,establish an Excel data table,and apply data mining software to The data is subjected to frequency statistics,association rules,cluster analysis and complex network analysis.Result:A total of 238 prescriptions for functional dyspepsia were screened.The four qi of the drugs were mainly warm and calm,the five flavors were mainly sweet and spicy,and the spleen and stomach were the main meridians.The top 10 Chinese medicines with higher frequency are Shanzha、Chenpi、Gancao、Maiya、Jineijin、Fuling、Baizhu、Shenqu、Houpo、Banxia;frequent itemsets show that the drugs are mainly compatible with qi and spleen,qi and digestion;association rules The analysis shows that the common drug pairs used in the treatment of functional dyspepsia include Chenpi-Shanzha、Maiya-Shanzha、Jineijin-Shanzha,etc.;cluster analysis found that there are 4 types of drugs for functional dyspepsia,mainly including drugs for regulating qi-flowing for harmonizing stomach,drugs for soothing liver and promoting Qi,drugs for eliminating food and resolving accumulation,drugs for benefiting qi and strengthening spleen;the 22-flavor Chinese medicine in the core drug network,the core compatibility is mainly to eliminate stagnation and spleen.Conclusion:Data mining research provides a reference for the clinical treatment of functional dyspepsia and the development of TCM formulas;Clinical treatment of functional dyspepsia should grasp the basic principles of strengthening vital energy and eliminating pathogenic factors to benefit qi,strengthen the spleen,and eliminate food.It is a basic treatment method,taking into account the methods of regulating qi-flowing for harmonizing stomach,soothing the liver and relieving depression,relieving dampness and dampness,and combining the specific conditions of patients with syndrome differentiation and treatment.

Characterization and kinetic modeling of secondary phases in squeeze cast Al alloy A380 by DSC thermal analysis

Thermal analyses on squeeze cast aluminum alloy A380(SC A380) solidified under 90MPa were carried out to study the microstructure development of the alloy, in which a differential scanning calorimeter(DSC) was employed. During the DSC runs, heating and cooling rates of 1, 3, 10, and 20 °C·min^(-1) were applied to investigate the heating and cooling effects on dissolution of secondary eutectic phases and microstructure evolution. Various reactions corresponding to troughs and peaks of the DSC curves were identified as corresponding to phase transformations taking place during dissolution or precipitation suggested by the principles of thermodynamics and kinetics. The comparison of the identified characteristic temperatures in the measured heating and cooling curves are generally in good agreement with the computed equilibrium temperatures. The microstructure analyses by scanning electron microscopy(SEM) with energy dispersive X-ray spectroscopy(EDS) indicate that the distribution and morphology of secondary phases present in the microstructure of the annealed sample are similar to the as-cast A380, i.e., strip β(Si), buck bone like or dot distributed θ(Al_2Cu), β(Al_5Fe Si) and Al_(15)(FeMn)_3Si_2. Two kinetic methods are employed to calculate the activation energies of the three common troughs and three common peaks in DSC curves of SC A380. The activation energies of the identified reaction θ_(CuAl_2) = α(Al)+β(Si) is 188.7 and 187.1 k J?mol^(-1) when the activation energies of reaction α(Al)+β(Si)→θCu Al_2 is^(-1)22.7 and^(-1)21.8 k J?mol^(-1), by the Kissinger and Starink methods, respectively.

Exploring the mechanisms of Jiangtang decoction in the treatment of diabetic nephropathy based on network pharmacology

Background:The purpose of this research is to predict the mechanisms of the experienced prescription Jiangtang decoction for treating diabetic nephropathy based on network pharmacology,the predicted targets and pathways were validated by celluar experiments.Methods:The active ingredients of the experienced prescription Jiangtang decoction and their putative targets were collected from TCMSP Database and SwissTargetPrediction platform.Diabetic nephropathy-related targets were excavated from GeneCards and DisGeNET database.Then,the interactions of potential targets of the experienced prescription Jiangtang decoction with well-known diabetic nephropathy targets were used to construct the protein-protein interaction network by STRING database and Cytoscape,and screened the core targets via topological analysis.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed by Metascape platform.Finally,we conducted in vitro experiments to verify this prediction of the network pharmacology.A diabetic nephropathy model was established by treating mesangial cells with D-ribose,in which the therapeutic effects of the experienced prescription Jiangtang decoction were evaluated.CCK-8 and LDH assay were used to test cell viability and cell toxicity,cell apoptosis was evaluated by Hoechst 33258 staining,AO/EB staining,levels of ROS were detected by fluorescent probe,the expression levels of MAPK signaling pathway-associated proteins and apoptosis-related proteins Bax were measured by western blotting assay.Results:A total of 74 active ingredients contained and 871 potential identified targets were retrieved from databases.Simultaneously,803 diabetic nephropathy-associated targets were also obtained,180 overlapped targets were considered as potential therapeutic targets of the experienced prescription Jiangtang decoction against diabetic nephropathy.By constructing a protein-protein interaction network and topological analysis,57 core targets were screened.Gene Ontology analysis highlighted 1655 Gene Ontology terms main including apoptotic signaling pathway,regulation of reactive oxygen species metabolic process and positive regulation of cell migration.KEGG enrichment analysis revealed that core targets were enriched mainly in MAPK,AGE-RAGE,TNF,PI3K-Akt signaling pathways.Cellular experiments further demonstrated D-ribose decreased mesangial cells viability,increased LDH release and the ROS level,induced apoptosis and activated the p38/JNK MAPK signal pathways,while the experienced prescription Jiangtang decoction could be useful in attenuation of D-ribose-induced damage.Conclusion:Network pharmacology intuitively shows the multi-component,multi-target and multi-pathway therapeutic effects of the experienced prescription Jiangtang decoction on diabetic nephropathy.By in vitro experiment,it revealed that the experienced prescription Jiangtang decoction has potential therapeutic effects on diabetic nephropathy via alleviating oxidative stress and apoptosis.the experienced prescription Jiangtang decoction treatment significantly inhibited the D-ribose-stimulated JNK and p38 MAPK activation.