BackgroundRecently, we have reported the induction of apoptosis by 2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-NC) in HepG2, T47D and HCT116 cells with low nano molar IC50 values. In this study, anti-proliferative effects of modified 4-aryle-4H-chromenes derivatives; 2-amino-4-(3-bromophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-BC), 2-amino-4-(3-trifluoromethylphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-TFC) and 2-amino-4-(4,5-methylenedioxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (4, 5-MC) were investigated in three human cancer cell lines. Compared to 3-NC none of the compounds displayed better anti-proliferative effect, although 3-BC appeared somewhat similar. Therefore 3-NC was selected for further studies.Methods and resultsTreatment of HepG2, T47D and HCT116 cells with this compound induced apoptosis as visualized by fluorescence microscopic study of Hoechst 33258 stained cells. Induction of apoptosis was quantified by Annexin V/PI staining using flow cytometry.Western blot analysis also revealed that 3-NC down-regulated the expression of anti-apoptotic protein Bcl2 and up-regulated pro-apoptotic protein Bax, in all of the cell lines. Nonetheless, HepG2 cell line was the most responsive to 3-NC as Bax and Bcl2 showed the most dramatic up and down regulation.ConclusionOur previous finding that 3-NC down regulates Inhibitor of Apoptosis Proteins (IAPs) and the present observation that Bax is upregulated and Bcl2 is down regulated upon 3-NC treatment, this chromene derivative has the potential to overcome chemotherapy resistance caused by up regulation of these proteins.
The current research was carried out to reveal the possible impacts of cold plasma on growth and physiology of wheat, as a new approach in plant science. Short and long-term impacts of different types of plasma (nitrogen and helium) with surface power density of 0.4 W cm-2 , exposure times (15, 30, 60, and 120 s), and repetitions (1, 2, and 4 times with 24 h intervals) were evaluated. Single-time applied helium or nitrogen derived plasma significantly promoted total root and shoot lengths, in contrast to four times application, and the root system was more sensitive than the shoot one. In addition, seedlings were more sensitive to nitrogen derived plasma, compared with helium. The physiological responses to plasma treatment were analyzed via protein assay and peroxidase or phenylalanine ammonia lyase (PAL) activities measurements. Plasma generated signaling molecules, especially ozone, nitric oxide, and/or UV radiation induced promotions in the peroxidase and PAL activities as well as increase in protein content in leaves, especially when times and/or repetitions increased. Plants were perished by the nitrogen derived plasma at the highest exposure time and number of repetitions. However, the seedlings with inhibited growth not only caught up control one month after, but even the growth rate and biomass accumulation in the shoot and leaves were accelerated. Increased leaf soluble phenol content was recorded in plasma treated seedlings, especially at longer times and more repetitions.
There seems to be a close relationship between hippocampal N-methyl-D-aspartic acid (NMDA) and GABAA receptors with respect to the modulation of behavior that occurs in the CA1 region of the hippocampus. This study investigated the possible involvement of the CA1 GABAA receptors in anxiolytic-like effects induced by (+)-MK-801 (a noncompetitive antagonist of the NMDA subtype of the glutamate receptor). Male Wistar rats were subjected to the elevated plus-maze apparatus and open arm time (%OAT), and open arm entries (%OAE) for anxiety-related behaviors, and closed arm entries that correspond to the locomotor activity were assessed. An intra-CA1 injection of (+)-MK-801 (2 μg/rat) and muscimol (0.5 μg/rat; a GABAA receptor agonist) increased %OAT and %OAE by themselves while not altering the closed arm entries, indicating an anxiolytic-like effect of these drugs. Injection of bicuculline (0.1, 0.25, and 0.5 μg/rat; a GABAA receptor antagonist) did not alter any of the anxiety-related parameters. An intra-CA1 injection of a subthreshold dose of muscimol (0.1 μg/rat) or bicuculline (0.5 μg/rat), 5 min before injection of subthreshold and effective doses of (+)-MK-801 (0.5, 1 and 2 μg/rat), increased and decreased the anxiolytic-like effect of (+)-MK-801, respectively. The isobologram analysis of these findings suggested a synergistic anxiety-like effect of intra-CA1 (+)-MK-801 and muscimol. In conclusion, the CA1 GABAA receptors appear to be involved in anxiolytic-like behaviors induced by (+)-MK-801.
Background: Gliosarcoma (GS) is a rare primary neoplasm of the central nervous system. It is a subtype of glioblastoma and has a biphasic pattern consisting of glial and malignant mesenchymal elements. Its onset is between the fourth and sixth decade of life.
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