NF-kB mediates acquired resistance in acute myeloid leukemia (AML) cells treated with DNA-damaging agents. Because DNA repair is the major molecular shift that alters sensitivity to DNA-damaging agents, we explored whether activation of the NF-kB pathway promotes AML cell survival by regulating DNA repair after chemotherapy. Our results showed that RELA, an important subunit of NF-kB, regulated DNA repair by binding to the promoter region of the PARP1 gene and affecting PARP1 gene transcription. Conversely, PARP1 knockdown reduced NF-kB activity, indicating that NF-kB and PARP1 create a positive feedback loop in DNA repair. Simultaneous treatment with the NF-kB inhibitor BMS-345541 and the PARP1 inhibitor olaparib resulted in robust killing of AML cells. This dual inhibition significantly suppressed tumor growth and extended survival times in xenograft tumor models. Implications: RELA and PARP1 form a positive feedback loop to regulate DNA damage repair, simultaneous inhibition of NF-kB and PARP1 increases the antileukemic efficacy of daunorubicin in vitro and in vivo, broadening the use of PARP1 inhibitors.
The number, type, strength, lifetime, and the exchange of hydrogen bonds in the self-healing process at different temperatures were investigated by molecular dynamics simulation using a micro-crack model.
Laparoscopy alone or combined with hysteroscopy can treat clinically stable interstitial pregnancy successfully. Transcervical suction using an 8 F pediatric catheter placed through the cornual end under laparoscopic and hysteroscopic guidance, preserving the uterus and fallopian tube, is an effective option for management of interstitial pregnancy in selected patients.
An intrinsic self-healing polyurethane (PU) elastomer was synthesized in our previous work. In this work, three-dimensional (3D) micro-crack models based on experimental samples were further introduced to investigate their self-healing...
Solubility parameters play an important role in predicting compatibility between components. The current study on solubility parameters of carbon materials (graphene, carbon nanotubes, and fullerene, etc.) is unsatisfactory and stagnant due to experimental limitations, especially the lack of a quantitative relationship between functional groups and solubility parameters. Fundamental understanding of the high-performance nanocomposites obtained by carbon material modification is scarce. Therefore, in the past, the trial and error method was often used for the modification of carbon materials, and no theory has been formed to guide the experiment. In this work, the effect of defects, size, and the number of walls on the Hildebrand solubility parameter (δ T ) of carbon nanotubes (CNTs) was investigated by molecular dynamics (MD) simulation. Besides, three-component Hansen solubility parameters (δ D , δ p , δ H ) were transformed into two-component solubility parameters (δ vdW , δ elec ). The quantitative relation between functional groups and two-component solubility parameters of single-walled carbon nanotubes (SWCNTs) was then given. An important finding is that the δ T and δ vdW of SWCNTs first decrease, reach a minimum, and then increase with increasing grafting ratio. The thermodynamic compatibility between functionalized SWCNTs and six typical polymers was investigated by the Flory−Huggins mixing model. Two-component solubility parameters were proven to be able to effectively predict their compatibility. Importantly, we theoretically gave the optimum grafting ratio at which the compatibility between functionalized SWCNTs and polymers is the best. The functionalization principle of SWCNTs toward good compatibility between SWCNTs and polymers was also given. This study gives a new insight into the solubility parameters of functionalized SWCNTs and provides theoretical guidance for the preparation of high-performance SWCNTs/polymers composites.
Temperature dependence of the interface between silica and styrene butadiene rubber modified by 3-mercaptopropionic acid was investigated by molecular dynamics simulation.
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