Thieno [2, 3-d] pyrimidine inhibits gastric cancer cell proliferation via the down-regulation of bcl-2 and survivin expressions

Purpose: To investigate the effect of thieno [2, 3-d] pyrimidine on gastric cancer (GC) cell proliferation, and elucidate the mechanism of action involved. Methods: Human GC cells (MKN1, MKN28 and SGC 7901) were cultured in RPMI-1640 medium supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/ streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. After attaining 60 - 70 % confluency, the cells were treated with serum-free medium and graded concentrations of thieno [2, 3-d] pyrimidine (0 – 12 µM) for 24 h. Normal cell culture without thieno [2, 3-d] pyrimidine served as control group. The cells were used in logarithmic growth phase. Cell viability and apoptosis were assessed using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The levels of expression of ZNF139, B cell lymphoma 2 (bcl-2) and survivin in MKN1 cells and orthotopically transplanted mice were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment of MKN1, MKN28 and SGC 7901 cells with thieno [2, 3-d] pyrimidine for 72 h led to significant and dose-dependent reductions in their viabilities, as well as significant and dose-dependent increases in the number of apoptotic cells (p < 0.05). The results of qRT-PCR and Western blotting showed that ZNF139 mRNA and protein expressions in MKN1 cells were significantly down-regulated by thieno [2, 3-d] pyrimidine treatment (p < 0.05). Thieno [2, 3-d] pyrimidine treatment significantly and dose-dependently down-regulated the expressions of bcl 2 and survivin proteins in MKN1 cells and orthotopically transplanted mice (p < 0.05). It also significantly and dose-dependently inhibited the proliferation of GC cells in orthotopic mouse model of GC after 31 days of treatment (p < 0.05). Conclusion: These results suggest that thieno [2, 3-d] pyrimidine suppresses the proliferation of GC cells via down-regulation of the expressions of ZNF139, bcl 2 and sur¬vivin. Thus, it has potentials for development for the management of gastric cancer

Bone marrow mesenchymal stem cells from leukemia patients inhibit growth and apoptosis in serum-deprived K562 cells

<p>Abstract</p> <p>Background</p> <p>The regulation of growth and apoptosis in K562 cells by human bone marrow mesenchymal stem cells (MSCs) from leukemia patients was investigated.</p> <p>Methods</p> <p>K562 cells were cocultured with leukemic MSCs under serum deprivation. Cell Counting Kit-8 (CCK-8), PI staining, Annexin V/PI binding and FACS assays were used to investigate cell proliferation, cell cycle status, and apoptosis of K562 cells cultures in the presence or absence of 10% serum. Western blotting was used to determine the levels of Akt, phosphorylated Akt (p-Akt), the BCL-2 family member Bad, and phosphorylated Bad (p-Bad) proteins in K562 cells after coculturing with MSCs. The effects of LY294002 (a specific inhibitor of PI3K) on protein expression were also determined.</p> <p>Results</p> <p>K562 cell proliferation was inhibited by coculture with MSCs and the dominant cell cycle was the G₀-G₁phase. The proportion of apoptotic K562 cells was decreased and the levels of p-Akt and p-Bad were upregulated after exposing K562 cells to MSCs. However, when LY294002 was used, p-Akt and p-Bad proteins inK562 cells showed a significant reduction, while no distinct variation was seen in the nonphosphorylated Akt and Bad protein levels.</p> <p>Conclusion</p> <p>Leukemic MSCs can inhibit K562 cell expansion and modulate the cell cycle to a state of relative quiescence. This allows the K562 cells to endure adverse conditions such as serum starvation. The PI3K-Akt-Bad signaling pathway may be involved in this antiapoptotic process via phosphorylation of the Akt and Bad proteins. Blocking MSC-induced transduction of the PI3K-Akt-Bad pathway may be a potential strategy for a targeted therapy to combat leukemia.</p

General synthesis of 2D rare-earth oxide single crystals with tailorable facets

Two-dimensional (2D) rare-earth oxides (REOs) are a large family of materials with various intriguing applications and precise facet control is essential for investigating new properties in the 2D limit. However, a bottleneck remains with regard to obtaining their 2D single crystals with specific facets because of the intrinsic non-layered structure and disparate thermodynamic stability of different facets. Herein, for the first time, we achieve the synthesis of a wide variety of high-quality 2D REO single crystals with tailorable facets via designing a hard-soft-acid-base couple for controlling the 2D nucleation of the predetermined facets and adjusting the growth mode and direction of crystals. Also, the facet-related magnetic properties of 2D REO single crystals were revealed. Our approach provides a foundation for further exploring other facet-dependent properties and various applications of 2D REO, as well as inspiration for the precise growth of other non-layered 2D materials

Constitutive behaviors of a silicone rubber at high strain rates

Silicone rubber is a macromolecule polymer, and can suffer a large deformation. In the paper, the silicone rubber specimens are tested at a series of strain rates by modified SHPB techniques. Based on the experimental data, a constitutive model of the silicone rubber is built up based on Ogden strain energy functions. An interesting phenomenon— localized damage cycle, so called lag circle— shows up in the tested specimen under high strain-rates loading. The diameters of the damage cycle are associated with strain-rate and specimen's size. A formulation about the relations between the diameter and the strain-rate, specimen's size is presented

Data Complexity: A New Perspective for Analyzing the Difficulty of Defect Prediction Tasks

Defect prediction is crucial for software quality assurance and has been extensively researched over recent decades. However, prior studies rarely focus on data complexity in defect prediction tasks, and even less on understanding the difficulties of these tasks from the perspective of data complexity. In this paper, we conduct an empirical study to estimate the hardness of over 33,000 instances, employing a set of measures to characterize the inherent difficulty of instances and the characteristics of defect datasets. Our findings indicate that: (1) instance hardness in both classes displays a right-skewed distribution, with the defective class exhibiting a more scattered distribution; (2) class overlap is the primary factor influencing instance hardness and can be characterized through feature, structural, instance, and multiresolution overlap; (3) no universal preprocessing technique is applicable to all datasets, and it may not consistently reduce data complexity, fortunately, dataset complexity measures can help identify suitable techniques for specific datasets; (4) integrating data complexity information into the learning process can enhance an algorithm's learning capacity. In summary, this empirical study highlights the crucial role of data complexity in defect prediction tasks, and provides a novel perspective for advancing research in defect prediction techniques

Research into the Energy Output of Asymmetric Cylindrical Structure under Internal Explosion Loading

The energy output characteristic of an asymmetric cylindrical structure under internal explosion loading has significant research value in the field of the national defense industry. This paper took the D-shaped structure as the research object. Three groups of experiments (D-90&deg;, D-120&deg;, D-150&deg;) were carried out. The D-shaped structure showed that fragments are concentrated in the middle and are sparse on both sides. Moreover, the fragment density decreased with the increase of the azimuth angle. The fragment velocities, which were measured from high-speed photography and an oscilloscope, coincided well with each other, and decreased with an increase in the central angle. Compared with the cylindrical structure, the fragment energy gain of the D-shaped structure is significant; the total energy and energy density of the three D-shaped structures were very close to each other. This indicates that D-120&deg; is the optimal solution among the three D-shaped structures and it can provide guidance for the future design of D-shaped structures to achieve higher energy output

Research on Irreversible Growth Mechanism of PBX due to Thermal Cycling

Current experiments show that the TATB-based polymer bonded explosives (PBX) will experience irreversible growth when suffered temperature cycling load. Although some studies have already been done on this, the cause of irreversible growth is still confusing, and the mechanism is not clear. In order to study the irreversible growth of PBX under temperature cycling load, an thermal-viscoelastic model is established, Based on the Burgers model which considering the influence of different temperatures on the creep properties of PBX. The analysis shows that the irreversible growth of PBX produced by the different creep properties of high and low temperature during the thermal cycling. Comparing with low temperature, the creep rate of PBX is faster and the deformation is larger at high temperature, which lead to the irreversible growth of PBX