The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium-binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may provide drugs with the potential to be used as multidrug resistance reversal agents with low toxicity and multi-target characteristics. The present study selected K562/DOX cells, a CML drug-resistant cell line, as a research model, and aimed to examine whether curcumin was able to reverse the resistance to doxorubicin (DOX), and elucidate the underlying molecular mechanisms. An MTT cytotoxicity assay indicated that curcumin at 0.5–2 µM reversed DOX resistance with a reversal index of 1.3–9.3. Western blot analysis revealed that curcumin treatment caused a downregulation of the expression of P-glycoprotein (P-gp) and S100A8 in a dose- and time-dependent manner. To study the internal association between S100A8 and P-gp, and the S100A8 role in drug resistance reversal, an RNA knockdown assay was conducted; however, S100A8 did not regulate the expression of P-gp or vice versa. After inhibiting the expression of S100A8 with specific small interfering RNA (si-S100A8), the sensitivity of K562/DOX cells to DOX was enhanced. In addition, si-S100A8 did not increase the intracellular accumulation of DOX, but increased the intracellular free calcium ion content, and the expression and activity of apoptosis-associated proteins, thereby inducing apoptosis. In conclusion, the present study suggested that inhibition of S100A8 expression increased DOX-induced apoptosis, and curcumin acted independently on S100A8 and P-gp to exert its drug resistance reversal effects
To study the failure modes, bearing capacity, ductility, and sleeve strain of grouted sleeve lapping connectors, 36 specimens were tested under uniaxial tensile load. The test results show that the sleeves are under longitudinal tension at the beginning, which changes to longitudinal compression in the late stage of loading, and the changing load increases gradually with the lap length. The force transmission path and mechanical mechanism of the connectors are analyzed. The distribution and development process of longitudinal sleeve stress is analyzed based on the constitutive model stress, and it is found that the sleeve changes from longitudinal tension to longitudinal compression at the late loading stage, which is consistent with the test results. Based on the test, the calculation formulas of the ultimate bond strength and critical lap length of the grouted sleeve lapping connector are proposed. The research results lay a theoretical foundation for the application of grouted sleeve lapping connectors.
In this study, uniaxial tension tests and high-stress repeated tension and compression tests were conducted on 32 APC (all vertical members precast in concrete structures) connectors. After high-stress repeated tension and compression, the bearing capacities of the connector specimens improved due to the strengthening of the steel bars, and the ductility of the specimens was reduced due to the further development of cracks between the steel bars and the grout. The residual deformation values of the specimens, namely u0 (uniaxial tension) and u20 (repeated tension and compression), were reduced with the increase in the lapping length of the specimens. The longitudinal compressive strain and hoop tensile strain of the middle section of the sleeve near the steel bar side were reduced under the ultimate load state when the specimens were stretched under uniaxial tension and in the last tension process after repeated loading with the increase in the lapping length. The distribution and development of the longitudinal compression stress of the sleeve were analysed based on the bonding stress of the steel bar and concrete. Finally, the ultimate bonding strength and critical lapping length formulas were proposed, which involved the introduction of a grouting defect coefficient ω.
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