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Magnesium transporter subtype 1 (MAGT1) is known to participate in animal development and cell differentiation. Thus far, MAGT1 studies have mainly focused on its role in cardiomyocyte regulation and differentiation; only a few studies have demonstrated its role in cell proliferation. To investigate the underlying mechanism of MAGT1 in cell proliferation, HeLa and SiHa cells were transiently knocked down with different siRNAs. We showed that cell proliferation was substantially restricted by S-phase arrest and apoptosis in the MAGT1-knocked down cells, which was further confirmed by the increased expression of p21, cyclin-A1, and cyclin-B1, as well as the decreased expression of MYC, cyclin-D1, cyclin-E1, and CDK2. MAGT1 knockdown also resulted in significant changes in the transcriptional expression of 1,598 genes that were analyzed by RNA sequencing. Bioinformatics analysis showed that MAGT1 was related to the MAPK signaling pathway. Western blot analysis confirmed that the phosphorylation of extracellular signal-related protein kinase 1/2 (ERK1/2) and p38 was remarkably reduced in MAGT1 down-regulated groups. Additionally, MAGT1 was required for the function of viral proteins E6/E7 during cell proliferation and G1/S cell-cycle progression. Therefore, MAGT1 plays a crucial role in the proliferation of HPV-positive cervical cancer cells, S-phase progression, and the ERK/p38 MAPK signaling pathway. These results indicate the potential of MAGT1 as a novel target for anticancer research. Abbreviations: MAGT1: Magnesium transporter subtype 1; MAPK: Mitogen-activated protein kinase; XMEN: X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia; BMMSCs: Bone Marrow Mesenchymal Stem Cells; Dpp: Decapentaplegic; CDKIs: CDK inhibitors; GPCR: G-protein coupled receptor; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; RTK: Receptor Tyrosine Kinase; PTK: Protein Tyrosine Kinase; FGFR: Fibroblast Growth Factor Receptor; BMP: Bone Morphogenetic Protein; HPV18 E6/E7: Human Papillomavirus 18 Early protein 6/ early protein 7; FACS: Fluorescence Activated Cell Sorting; PI: Propidium Iodide [ABSTRACT FROM AUTHOR]

Tissue engineering technology provides effective alternative treatments for tracheal reconstruction. The formation of a functional microvascular network is essential to support cell metabolism and ensure the long-term survival of grafts. Although several tracheal replacement therapy strategies have been developed in the past, the critical significance of the formation of microvascular networks in 3D scaffolds has not attracted sufficient attention. Here, we review key technologies and related factors of microvascular network construction in tissue-engineered trachea and explore optimized preparation processes of vascularized functional tissues for clinical applications. [ABSTRACT FROM AUTHOR]

Tissue scaffolds need to have anisotropic mechanical properties and a porous structure to meet the needs of different tissues and organs. This report presents results of a study on an especially-designed 3D printing method with oxidized nanocellulose and gelatin, analyzes the servo principle of pneumatic condensing extrusion 3D printer, and proposes a hexagonal algorithm. For the purpose of this study, a printing process file was written by G code, physical and mechanical performance of the 3D scaffolds was evaluated with Solidworks simulation, the porous structure and pressure-pull performance of the printed 3D scaffolds was observed by SEM, and experiments were conducted to measure their bio-compatibility. The study draws the conclusion that scaffolds thus printed have a highly porous structure and anisotropic mechanical properties. [ABSTRACT FROM AUTHOR]

For tissue engineering applications tissue scaffolds need to have a porous structure to meet the needs of cell proliferation/differentiation, vascularisation and sufficient mechanical strength for the specific tissue. Here we report the results of a study of the 3D printing process for composite materials based on oxidized nanocellulose and gelatin, that was optimised through measuring rheological properties of different batches of materials after different crosslinking times, simulation of the pneumatic extrusion process and 3D scaffolds fabrication with Solidworks Flow Simulation, observation of its porous structure by SEM, measurement of pressure-pull performance, and experiments aimed at finding out the vitro cytotoxicity and cell morphology. The materials printed are highly porous scaffolds with good mechanical properties. [ABSTRACT FROM AUTHOR]

Abstract: To prepare an NCECS/nHA composite for tissue-engineered trachea and investigate its biomechanical and biocompatibile properties. Biomechanical tests were performed on dry and wet NCECS/nHA composite specimens prepared in vitro. The cell adhesion rate on each composite surface after 2, 6, and 12 hours of culture was calculated, and cell proliferation activity was measured using an MTT assay. NCECS/nHA composites exhibited satisfactory tensile strength and Young's modulus values. The adhesion rate of rabbit tracheal chondrocytes on NCECS/nHA surfaces reached 88.4% after 12 hours of culture. NCECS/nHA composites are promising scaffold materials for tissue-engineered trachea owing to satisfactory biocompatible and biomechanical properties. [ABSTRACT FROM AUTHOR]

Aim: Multidrug resistance (MDR) is closely correlated to an unfavorable prognosis in various human cancers. However, the clinical significance of the expression of MDR-related proteins p-glycoprotein (PGP), glutathione-s-transferases (GST-π), topoisomerase-II (Topo-II) and lung resistance protein (LRP) in primary gastric cardiac adenocarcinoma (PGCA) remains unclear. In this present study, the total of the four kinds of MDR-related proteins mentioned above were detected by using immunohistochemistry, and their clinical significance in chemoresistance were also investigated. Methods: This retrospective study included 69 resected specimens from patients with PGCA. The expression of PGP, GST-π, Topo-II and LRP in formalin-fixed paraffin-embedded tissue sections was determined by a labelled streptavidin-biotin immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results: The positive rates of expression of PGP, GST-π, Topo-II and LRP in malignant tissues (49.2%, 75.4%, 68.1% and 58%, respectively) were all higher than that of the normal tissues(0, 30%, 20% and 0, respectively, P < 0.01). PGP expression in tumors that had metastasized was significantly more frequent than in tumors that had not metastasized (67.5% vs 24.1%, P < 0.01). The expression of PGP was closely related with clinicopathologic staging (staging 1/2 vs 3/4, 28.6% vs 58.3%, P < 0.05). No significant correlation was shown between PGP and increasing differentiated degree (40%, 42.4% and 61.5%, P > 0.05). GST-π expression status progressively increased with increasing differentiated degree (40%, 75.8% and 88.5%, P < 0.05) and clinicopathologic stage (staging 1/2 vs 3/4, 57.1% vs 83.3%, P < 0.05). In addition, a significant positive correlation was also observed between GST-π and lymphatic metastasis (with vs. without metastasis, 87.5% vs 58.6%, P < 0.05). The expression of Topo-II was associated with increasing differentiated degree (33.3%, 69.7 and 80.7%, P < 0.01). No significant differences with Topo-II expression were found in relation to the clinicopathologic stage (staging 1/2 vs 3/4, 57.1% vs 72.9%, P > 0.05) and lymphatic metastasis (with vs. without metastasis, 65.0% vs 72.4%, P > 0.05). Moreover, a significant difference with the expression of LRP was found in relation to the clinicopathologic stage (staging 1/2 vs 3/4, 38% vs 66.6%, P < 0.05), and lymphatic metastasis (with vs without metastasis, 70.0% vs 41.4%, P < 0.05). Comparing the well, moderately and poorly differentiated cohort, a non-statistical increasing trend towards LRP expression status was noted (50.0%, 54.5% and 65.3%, respectively, P > 0.05). Besides, the co-expression of all four tested MDR-related proteins also existed. The positive rates of co-expression of PGP and GST-π, PGP and Topo-II, PGP and LRP, GST-π and Topo-II, LRP and GST-π, LRP and Topo-II, PGP, GST-π, Topo-II and LRP in malignant cells were 23.2%, 15.9%, 11.6%, 13.0, 26.1, 7.24, 5.8, respectively. Conclusions: MDR-related proteins PGP, GST-π, Topo-II α and LRP are involved in multiple mechanisms of drug resistance in PGCA. Combined determination of PGP, GST-π, Topo-II and LRP may be prospectively valuable for optimizing the chemotherapy regimes, developing high quality anti-cancer drugs, and further predicting the outcomes of those patients with PGCA. [ABSTRACT FROM AUTHOR]