RESUMEN
Previous studies indicate that traditional asphalt mixtures lack the ability to withstand the stresses caused by heavy traffic volumes under high temperatures. To enhance the rutting resistance of flexible pavement under high levels of temperature and loading, extensive laboratory experiments were carried out. A 60/70 grade bitumen was used as a neat sample for comparison. The study introduced three distinct polymers, polypropylene (PP), low-density polyethylene (LDPE), and acrylonitrile butadiene styrene (ABS), at varying concentrations by weight into the neat bitumen. Initially, conventional tests were performed to evaluate the conventional properties of both the neat and modified bitumen, while aggregate tests assessed the mechanical properties of the aggregates. Subsequently, a Marshall mix design was performed to determine the optimum bitumen content (OBC) in the asphalt mixture. Finally, wheel-tracking tests were performed under a specific load and temperature to investigate the rutting behavior of the modified asphalt mixtures. The results of this comprehensive study revealed that the modified asphalt mixtures displayed improved resistance to rutting compared to the neat asphalt mixture. Furthermore, it was also observed that the LDPE exhibited a superior performance against rutting, followed by the PP and ABS. At polymer contents of 3%, 5%, and 7%, the LDPE achieved reductions in rut depth of 13%, 24%, and 33%, respectively, outperforming both PP- and ABS-modified asphalt. These findings not only enhance our understanding of asphalt behavior under diverse conditions but also highlight the potential of plastic-modified asphalt as an effective solution for mitigating rutting problems in road pavements. By incorporating plastic modifiers into asphalt mixtures, this approach aligns with the principles of sustainable construction by reducing plastic waste while improving pavement durability and performance.
RESUMEN
PURPOSE: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin. METHODS: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780cisR (cisplatin resistant) and A2780ZD0473R. Resistance factor (RF) of drugs was determined in these three cell lines. Combination index (CI) was calculated as a measure of combined drug action. Effect of this combination on changes in the cellular accumulation of platinum levels and platinum-DNA binding was also determined in vitro using AutoDock Vina while the effect of wedelolactone on inhibition of possible key culprits of resistance including Chk1, CD73, AT tip60, Nrf2, Brd1, PCAF, IGF1, mTOR1 and HIF2α was investigated in silico. RESULTS: Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780cisR showing its potential to bring more cell death in cisplatin-resistant cells. CI values were found to vary showing antagonistic to additive outcomes. Additive effect was observed for all sequences of administration (0/0, 0/4 and 4/0 h) in A2780cisR. Enhanced cellular accumulation of cisplatin was observed in parent and resistant cells on combination. Docking results revealed that among the selected oncotargets, Chk1, CD73, Nrf2, PCAF and AT tip60 were more vulnerable to wedelolactone than their respective standard inhibitors. CONCLUSION: These findings have shown that additive outcome of drug combination in A2780cisR and raised levels of platinum accumulation followed a clear pattern. This observation indicates that the presence of wedelolactone might have contributed to sensitize A2780cisR. However, in silico results point to the possible effects of this compound on epigenetic factors involving tumor microenvironment, epithelial mesenchymal transition, and immune-checkpoint kinases.