TASK DEFINITION: Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
PROBLEM: The aim of this study was to investigate the antiproliferative and cytotoxic effects of a newly synthesized molecule named paracetamol acetohydroxamic acid (PaCaHa) on human neoplastic cell lines.', 'A549, CRL 2923, HeLa, and ARPE were treated with various concentrations of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa were determined after a 24-h incubation period and compared to the DMSO control. The cytotoxic and antiproliferative effects were determined by the trypan blue dye exclusion and MTT methods.', 'A higher susceptibility to PaCaHA was found in CRL 2923 and HeLa cells, while A549 and ARPE cells were less responsive to PaCaHa. The percent of cytotoxicity resulting from 400 µg/mL of PaCaHa were >90 for CRL-2923 and HeLa, 68 for A549, and 64 for ARPE cells. The cytotoxic difference between CRL-2923/HeLa and ARPE/A549 cells was significant (P < 0.05).

SOLUTION: 1

PROBLEM: To investigate the effect of targeted antiosteosarcoma methotrexate-bisphosphonate conjugate on growth inhibition and apoptosis in human osteosarcoma MG-63 cells.', 'MG-63 cells were treated with various concentrations of methotrexate-bisphosphonate conjugate and apoptosis was monitored via an MTT assay, cell morphology, TUNEL assay and flow cytometry analysis.', 'The survival rate of MG-63 cells treated for 24 to 96 hours with 2000 mg/ml or more of methotrexate-bisphosphonate conjugate decreased significantly. Cells treated with conjugate showed typical apoptotic features using inverted phase contrast microscopy and fluorescence staining, and the majority of cells demonstrated a positive result in the TUNEL assay. Karyopyknosis and crescent aggregation of chromatin were observed in conjugate-treated cells by electron microscopy. Flow cytometry of MG-63 cells treated with methotrexate-bisphosphonate conjugate showed a time and dose-dependent increase in apoptosis (p < 0.05).

SOLUTION: 1

PROBLEM: Apoptosis of cardiomyocytes may contribute to ischemia-reperfusion injury. The role of nitric oxide (NO) in apoptosis is controversial. Therefore, we investigated the effect of NO synthase inhibition on apoptosis of cardiomyocytes during ischemia and reperfusion and elucidated the underlying mechanisms.', 'Isolated perfused rat hearts (n = 6/group) were subjected to ischemia (30 min) and reperfusion (30 min) in the presence or absence of the NO synthase inhibitor NG-mono-methyl-L-arginine. Reperfusion induced cardiomyocyte apoptosis as assessed by immunohistochemistry (TUNEL-staining) and the demonstration of the typical DNA laddering. Apoptosis during reperfusion was associated with the cleavage of caspase-3, the final down-stream executioner caspase, whereas the protein levels of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax were unchanged. Inhibition of the NO synthase drastically increased ischemia and reperfusion-induced apoptosis of cardiomyocytes. Moreover, the NO synthase inhibitor enhanced the activation of caspase-3, suggesting that NO interferes with the activation of caspases in ischemia-reperfusion.

SOLUTION:
1