Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice. Pten KO mice were assigned to a control group without any medication or to a 1,8-cineole group injected with 50 mg/kg i.p. twice per week for eight weeks. At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining. Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis. Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway. 相似文献
This paper deals with the transient behavior of a flame flowing into a narrow channel from a chamber filled with a propane---air mixture.
The flame was observed through direct or schlieren high speed photography, and at the same time the arrival at the entrance and exit of the channel were detected by ion gaps. From the experimental results it was found that in some cases the flame extinguished or hesitated in the channel before passing through. These behaviors were dependent on the equivalence ratio of the mixture, the channel width, and the flame inflow velocity.
Flame standstill in the channel is assumed to be caused by continuous quenching of hot reacting gas due to turbulent mixing with cold unburned gas at the contraction region established near the entrance of the channel. For any specific mixture, when the channel entrance is rounded or the inflow velocity is low, the minimum width of the channel for which a flame will run through without any retardation becomes smaller compared with the case of a sharp-edged entrance or a high inflow velocity. On the contrary, the minimum width of the channel for which a flame cannot pass through does not depend on the corner roundness of the channel entrance or the inflow gas velocity. 相似文献
Senolytic agents eliminate senescent cells and are expected to reduce senescent cell-mediated adverse effects in cancer therapy. However, the effects of senolytic agents on the survival of irradiated cancer cells remain unknown. Here, the effects of the senolytic agent ABT-263 on the survival of irradiated A549 and Ca9-22 cancer cells were investigated. ABT-263 was added to the culture medium after irradiation. SA-β-gal activity and cell size, which are hallmarks of cell senescence, were evaluated using a flow cytometer. The colony-forming assay and annexin V staining were performed to test cell survival. We first confirmed that radiation increased the proportion of cells with high SA-β-gal activity and that ABT-263 decreased it. Of note, ABT-263 decreased the survival of irradiated cancer cells and increased the proportion of radiation-induced annexin V+ cells. Furthermore, the caspase inhibitor suppressed the ABT-263-induced decrease in the survival of irradiated cells. Intriguingly, ABT-263 decreased the proportion of SA-β-gal low-activity/large cells in the irradiated A549 cells, which was recovered by the caspase inhibitor. Together, these findings suggest that populations maintaining the ability to proliferate existed among the irradiated cancer cells showing senescence-related features and that ABT-263 eliminated the population, which led to decreased survival of irradiated cancer cells. 相似文献
Administration of recombinant interleukin 12 (IL-12) induces tumor regression that is associated with T-cell infiltration in the OV-HM ovarian carcinoma and CSA1M fibrosarcoma models. After confirming the blocking of regression by injection of anti-IFN-gamma monoclonal antibody (mAb), we investigated the mechanisms underlying the requirement of IFN-gamma in T-cell migration and tumor regression. T-cell migration was inhibited by injection of anti-IFN-gamma mAb to OV-HM tumor-bearing mice prior to IL-12 treatment. We examined, using the lymphoid cell migration assay, whether IFN-gamma is required for enhancing the migratory capacity of T cells or the T cell-accepting potential of tumor masses during IL-12 treatment. Spleen cells from IL-12-treated or untreated OV-HM-bearing mice were stained in vitro with a fluorescein chemical and transferred i.v. into OV-HM-bearing mice that were not treated with IL-12. Migration of donor cells was quantitated by counting the number of fluorescent cells on cryostat sections of tumor masses from recipient mice. Compared to spleen cells from OV-HM-bearing mice that were not treated with IL-12, enhanced migration was observed for cells from IL-12-treated OV-HM-bearing mice. Anti-IFN-gamma pretreatment of donor mice before IL-12 treatment did not reduce the migratory capacity of T cells, whereas migration was markedly inhibited in recipient mice injected with anti-IFN-gamma. Anti-IFN-gamma pretreatment decreased vascular cell adhesion molecule-1 (VCAM-1)-/intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels at tumor sites. Consistent with this, migration was also inhibited by treatment of recipient mice with either anti-VCAM-1 or anti-ICAM-1 mAb. In contrast to the OV-HM model, T-cell migration was not affected in the CSA1M model following preinjection of anti-IFN-gamma mAb. In this model, VCAM-1-/ICAM-1-positive blood vessels existed even after anti-IFN-gamma treatment, although tumor regression was completely inhibited. These results indicate that IFN-gamma plays two distinct roles in expressing the antitumor efficacy of IL-12: one is to support the T-cell acceptability of tumor masses, and the other is to mediate the antitumor effects of migrated T cells. 相似文献
OBJECT: Tamoxifen (TAM) has been found to be effective in inhibiting proliferation of glioblastoma cells in vitro, but clinical studies have been disappointing. The purpose of this study was to determine whether insulin-like growth factor I (IGF-I), a potential autocrine/paracrine mitogen produced by glioblastomas, interferes with the antimitogenic actions of TAM. METHODS: Human glioblastoma cells were treated with or without TAM and/or IGF-I in vitro and evaluated for: viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide cleavage assay; apoptosis by histochemical analysis of nuclear morphology and 3'-OH DNA fragments; and expression of the IGF-I receptor, and the bcl-2, bcl-xL, and bax proteins by immunoblot analysis. In addition, p53 status was determined by DNA sequencing and by transient transfection with luciferase reporter plasmids containing wild-type or mutant p53. Results indicated that after 72 hours of exposure to 2 mg/ml TAM in vitro, 56.3% of WITG3 and 43.8% of U87-MG glioblastoma cells contained apoptotic nuclei (p < 0.01 compared with untreated cells). Apoptosis was independent of the presence of p53 because the WITG3 cells, in contrast to the U87-MG cells, expressed a mutant, nonfunctional p53. The WITG3 cells expressed IGF-I receptor proteins and demonstrated IGF-I binding. Exogenous IGF-I stimulated WITG3 cell proliferation and significantly (p < 0.05) antagonized the cytotoxic effects of TAM in a dose-dependent fashion; IGF-I, but not TAM, enhanced expression of bcl-2 and bcl-xL proteins; however, bax protein expression was unchanged by either treatment. CONCLUSIONS: Because many gliomas secrete large amounts of IGF-I in autocrine/paracrine growth pathways, these data may, in part, explain the failure of TAM to achieve clinical results as dramatic as those in vitro. 相似文献
Journal of Porous Materials - A carbon molecular sieve (CMS) membrane is a microporous membrane that can serve as a molecular sieve. Tuning the pore size of a CMS membrane to improve the... 相似文献
High‐mobility and highly reliable self‐aligned top‐gate oxide thin‐film transistor (TFTs) were developed using the aluminum reaction method. Al diffusion to the oxide semiconductor and homogenization of the oxygen concentration in the depth direction after annealing were confirmed by laser‐assisted atom probe tomography. The high mobility of the top‐gate TFT with amorphous indium tin zinc oxide channel was demonstrated to be 32 cm2/V s. A 9.9‐in. diagonal qHD active‐matrix organic light‐emitting diode (AM‐OLED) display was fabricated using a five‐mask backplane process to demonstrate an applicable solution for large‐sized and high‐resolution AM‐OLEDs. 相似文献
A novel technique for post-thinning of lifted-out membranes already mounted on a mesh was developed using a Ga(+) ion beam at an accelerating voltage of 5 kV. It was applied to the preparation of transmission electron microscopy specimens from a selected cell of a silicon dynamic random-access memory. 相似文献
The structure and rheological properties of heat‐ and pressure‐induced myosin filament gels were investigated. The apparent elasticity of heat‐induced gel peaked at 55 °C (4.35 ± 0.57 kPa), whereas that of pressure‐induced gel increased with elevating pressure, and the gel formed at 500 MPa had a value of 4.79 ± 0.25 kPa. All pressure‐ and heat‐induced gels showed similar internal structure, namely, the gels were composed of a fine‐strand network. The detailed structures of the strands induced by pressure‐ and heat‐treatment of myosin filaments were observed using an atomic force microscope. The structural differences among the strands were not observed, whereas the elasticity of the strands measured by atomic force microscope revealed differences among the strands formed with varying heating temperature and pressure. The elasticities of the heat‐induced strands were 1.19 ± 0.09 MPa, 10.24 ± 1.16 MPa, and 3.09 ± 0.25 MPa at 40 °C, 55 °C, and 70 °C, respectively. On the other hand, the elasticity of the pressure‐induced strand increased with elevating pressure. The elasticity values were 1.24 ± 0.09 MPa, 2.32 ± 0.17 MPa, and 9.80 ± 0.84 MPa at pressures of 150, 300, and 500 MPa, respectively. Because the changes in the elasticity of the whole gel corresponded to those of the strand, it is concluded that the rheological properties of the constituting strands determine that of myosin filamentous gel. 相似文献