The chemotherapy of tumors is frequently limited by the development of resistance and severe side effects. Phytochemicals may offer promising candidates to meet the urgent requirement for new anticancer drugs. We screened 69 phytochemicals, and focused on gedunin to analyze its molecular modes of action. Pearson test-base correlation analyses of the log10IC50 values of 55 tumor cell lines of the National Cancer Institute (NCI), USA, for gedunin with those of 91 standard anticancer agents revealed statistically significant relationships to all 10 tested microtubule inhibitors. Thus, we hypothesized that gedunin may be a novel microtubule inhibitor. Confocal microscopy, cell cycle measurements, and molecular docking in silico substantiated our assumption. Agglomerative cluster analyses and the heat map generation of proteomic data revealed a subset of 40 out of 3171 proteins, the expression of which significantly correlated with sensitivity or resistance for the NCI cell line panel to gedunin. This indicates the complexity of gedunin’s activity against cancer cells, underscoring the value of network pharmacological techniques for the investigation of the molecular modes of drug action. Finally, we correlated the transcriptome-wide mRNA expression of known drug resistance mechanism (ABC transporter, oncogenes, tumor suppressors) log10IC50 values for gedunin. We did not find significant correlations, indicating that gedunin’s anticancer activity might not be hampered by classical drug resistance mechanisms. In conclusion, gedunin is a novel microtubule-inhibiting drug candidate which is not involved in multidrug resistance mechanisms such as other clinically established mitotic spindle poisons.

On incidence of kidney failure, the concentration of urea increases and there is need for patients to visit the hospital all through the week for blood purification. However, current hemodialysis has been found to reduce only 66‐75% urea in the blood of patients. The main goal of this article is to observe the effect of biocompatible and high mechanical hemodiafiltration in reducing urea and creatinine within the shortest time frame, using two methods of Nano electrospinning fiber (hybrid and coaxial). Hybrid electrospinning was made by zeolite 940‐HOA(beta), Fe3O4, polyacrylonitrile as well as the addition of nettle plant's leaf extract. Dispersing solution and enzymes were added to two different syringes and was used in making hybrid nanofibers by the electrospinning process. Nessler's Reagent adsorption method was used for measuring the concentration of ammonia after urease enzyme activation. Second coaxial filter was made by the core‐shell electrospinning system and cellulose acetate phthalate (CAP) as well as polyurethane (PU) were utilized. The data show hybrid hemodiafiltration with enzyme coating, decomposed urea and enzymes were activated for two days after electrospinning. The core‐shell filtration can also reduce creatinine. Core‐shell CAP‐PU nanofiber was previously used for intravaginal drug delivery and PU was used as an artificial renal microfluidic chip. Thus, our study focused on using CAP‐PU to reduce creatinine in dialysis patients. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1736–1743, 2019.

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