About 20% of patients with chronic myeloid leukemia (CML) do not respond to treatment with imatinib either initially or because of acquired resistance. To study the development of CML drug resistance, an in vitro experimental system comprising cell lines with different resistance levels was established by exposing K562 cells to increasing concentrations of imatinib and dasatinib anticancer agents. The mRNA levels of BCR- ABL1 and of genes involved in drug transport or redistribution (ABCB1, ABCC1, ABCC3, ABCG2, MVP, and SLC22A1) were measured and the ABL1 kinase domain sequenced. Results excluded BCR- ABL1 overexpression and mutations as relevant resistance mechanisms. Most studied transporters were overexpressed in the majority of resistant cell lines. Their expression pattern was dynamic: varying with resistance level and chronic drug exposure. Studied efflux transporters may have an important role at the initial stages of resistance, but after prolonged exposure and for higher doses of drugs other mechanisms might take place.

Despite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms. A relationship between the type of BCR-ABL1 transcript or ABCB1 or SLC22A1 genotype and response to treatment was not discovered. However, the studied genes had higher expression levels in follow-up compared to the diagnostic samples, demonstrating a possible induction in expression. IM-sensitive patients presented significantly higher values of SLC22A1 expression, suggesting higher drug influx. Most importantly, while responding patients demonstrated stable expression signatures in consecutive samples, there was considerable variation in IM-resistant patients, indicating that single point sampling expression signatures are not reliable in predicting clinical outcomes or prognostic features in these patients. Studies that assessed consecutive samples from CML patients in order to evaluate the variation in expression levels of transporter genes are limited yet our study emphasizes the importance of such approaches.

We concluded that all the benzoates could be activated by mycobacterial enzymes and the esters presented higher activity than the corresponding free acids, with the nitrobenzoates, and specially the dinitrobenzoates, showing very interesting antitubercular activity that deserve further exploration. These results do not show a correlation between the activity and the pKa of the acids.

Multifunctional materials and devices with captivating properties can be assembled from cellulose and cellulose-based composite materials combining functionality with structural performance. Cellulose is one of the most abundant renewable materials with captivating properties, such as mechanical robustness, biocompatibility, and biodegradability. Cellulose is a low-cost and abundant biodegradable resource, CO2 neutral, with a wide variety of fibers available all over the world. Over thousands of years, nature has perfected cellulose-based materials according to their needs, such as function vs. structure. Mimicking molecular structures at the nano-, micro-, and macroscales existing in nature is a great strategy to produce synthetic cellulose-based active materials. A concise background of cellulose and its structural organization, as well as the nomenclature of cellulose nanomaterials, are first addressed. Key examples of nature-designed materials with unique characteristics, such as “eternal” coloration and water-induced movement are presented. The production of biomimetic fiber and 2D fiber-based cellulosic materials that have attracted significant attention within the scientific community are represented. Nature-inspired materials with a focus on functionality and response to an external stimulus are reported. Some examples of 3D-printed cellulosic materials bioinspired, reported recently in the literature, are addressed. Finally, printed cellulosic materials that morph from a 1D strand or 2D surface into a 3D shape, in response to an external stimulus, are reported. The purpose of this review is to discuss the most recent developments in the field of “nature-inspired” cellulose-based active materials regarding design, manufacturing, and inspirational sources that feature existing tendencies.