Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer

Purpose: To investigate the antitumor and chemoresistance-lowering effects of pectolinarigenin on breast cancer cells.Methods: Pectolinarigenin was purified by a combination of silica gel and Sephadex LH-20 column chromatography from ethanol extracts of the aerial parts of C. japonicum DC. Breast cancer selfrenewal properties were tested by colony formation and tumor sphere formation assays. Thereafter, real-time polymerase chain reaction (PCR) was used to detect breast cancer stem cell markers. Furthermore, the effect of pectolinarigenin on breast cancer cell was evaluated by chemoresistance using 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Finally, tumor formation in nude mice was used to test the effect of pectolinarigenin on tumorigenicity of breast cancer cells in vivo.Results: The results showed that pectolinarigenin, extracted from Cirsium japonicum Fisch. ex DC., inhibited tumor cell self-renewal in MCF-7 breast cancer cells. Pectolinarigenin (25 μM) caused significant inhibition of colony formation (61.23 %, p < 0.001) and tumor sphere formation (59.49 %, p < 0.01) in MCF-7. The inhibitory effects were associated with changes in breast cancer stem cell markers. Treatment of breast cancer cells with pectolinarigenin reduced the chemoresistance of the cells to doxorubicin. At the same time, mRNA expression of chemoresistance genes (ATP binding cassette subfamily G member 2, ABCG2 and ATP binding cassette subfamily B member 1, MDR1) was repressed by pectolinarigenin. The inhibition efficiency of MDR1 and ABCG2 by 10 μM pectolinarigenin treatment was about 59.29 (p < 0.01) and 46.48 % (p < 0.01), respectively. Furthermore, pectolinarigenin reduced tumor mass in nude mice xenograft model.Conclusion: Pectolinarigenin inhibits breast cancer stem cell-like properties and lowers the chemoresistance of the cancer cells to chemotherapy. The results provide an insight into the mechanism of the anti-breast tumor effects and an experimental basis for the use of pectolinarigenin to enhance treatment of patients with breast cancer.Keywords: Pectolinarigenin, Cancer stem cells, Breast cancer, Chemoresistance, Cirsium japonicum Fisch. ex D

Effects of Molecular Structure and Packing Order on the Stretchability of Semicrystalline Conjugated Poly(Tetrathienoacene-diketopyrrolopyrrole) Polymers

The design of polymer semiconductors possessing high charge transport performance, coupled with good ductility, remains a challenge. Understanding the distribution and behavior of both crystalline domains and amorphous regions in conjugated polymer films, upon an applied stress, shall provide general guiding principles to design stretchable organic semiconductors. Structure–property relationships (especially in both side chain and backbone engineering) are investigated for a series of poly(tetrathienoacene-diketopyrrolopyrrole) polymers. It is observed that the fused thiophene diketopyrrolopyrrole-based polymer, when incorporated with branched side chains and an additional thiophene spacer in the backbone, exhibits improved mechanical endurance and, in addition, does not show crack propagation until 40% strain. Furthermore, this polymer exhibits a hole mobility of 0.1 cm2 V−1 s−1 even at 100% strain or after recovered from strain, which reveals prominent continuity and viscoelasticity of the polymer thin film. It is also observed that the molecular packing orientations (either edge-on or face-on) significantly affect the mechanical compliance of the polymer films. The improved stretchability of the polymers is attributed to both the presence of soft amorphous regions and the intrinsic packing arrangement of its crystalline domains

Integrin Targeted MR Imaging

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models.</p

Characteristic Analysis of Digital Emulsion Relief Valve Based on the Hydraulic Loading System

In the hydraulic loading system, the performance of digital relief valve plays an important role in the dynamic response of load. However, the research on large-flow emulsion relief valve is still far from perfect. In this paper, digital relief valve is taken as the research object. Based on pilot-operated relief valve, a digital control scheme using a linear stepping motor is adopted to regulate the working pressure of relief valve. The structure of relief valve is analyzed and optimized from the aspects of dynamic and internal flow field characteristics to obtain a good working performance. To obtain its accurate working characteristic, the structural model and digital control system of relief valve are established by AMESim and Simulink, respectively, for electrohydraulic cosimulation. The results show that digital relief valve has a better characteristic of real-time dynamic pressure regulation. Therefore, the digital control system could improve the dynamic performance of relief valve, and the design of digital relief valve structure is reasonable and feasible. The simulation method employed in this paper provides a better theoretical basis and reference for the comprehensive research of digital large-flow emulsion relief valves based on the hydraulic loading system

Identification Of Putative Gene Signatures Associated With Diagnosis And Prognosis Of Breast Cancer

Purpose: This study aimed to identify potential diagnostic and therapeutic biomakers for the development ofbreast cancer (BC). Methods: GSE86374 dataset containing 159 samples was acquired from the Gene Expression Omnibus (GEO) database followed by differentially expressed genes (DEGs) identification and cluster analysis. Corresponding functional enrichment and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Prognostic evaluation using clinical information obtained from TCGA database and hub genes was conducted to screen for crucial indicators for BC progression. The risk model was established and validated. Results: In total, 186 DEGs were identified and grouped into four clusters: 96 in cluster 1; 69 in cluster 2; 16 in  cluster 3; and 5 in cluster 4. Functional enrichment analysis showed that DEGs, including ADH1B in cluster 1,  were dramatically enriched in the tyrosine and drug metabolism pathways, while genes in cluster 2, including  SPP1 and RRM2, played crucial roles in PI3K-Akt and p53 signalling pathway. SPP1 and RRM2 served as hub  genes in the PPI network, resulting in an support vector machine classifier with good accuracy and specificity.Ad ditionally, the results of prognostic analysis suggest that age, metastasis stage, SPP1 and ADH1B were correlated with risk of BC, which was validated by using the established risk model analysis. Conclusion: SPP1, RRM2 and ADH1B appear to play vital roles in the development of BC. Age and TNM stage  were also preferentially associated with risk of developing BC. Evaluation of the risk model based on larger sample size and further experimental validation are required