MSCs as Tumor-Specific Vectors for the Delivery of Anticancer Agents—A Potential Therapeutic Strategy in Cancer Diseases: Perspectives for Quinazoline Derivatives

Mesenchymal stem cells (MSCs) are considered to be a powerful tool in the treatment of various diseases. Scientists are particularly interested in the possibility of using MSCs in cancer therapy. The research carried out so far has shown that MSCs possess both potential pro-oncogenic and anti-oncogenic properties. It has been confirmed that MSCs can regulate tumor cell growth through a paracrine mechanism, and molecules secreted by MSCs can promote or block a variety of signaling pathways. These findings may be crucial in the development of new MSC-based cell therapeutic strategies. The abilities of MSCs such as tumor tropism, deep migration and immune evasion have evoked considerable interest in their use as tumor-specific vectors for small-molecule anticancer agents. Studies have shown that MSCs can be successfully loaded with chemotherapeutic drugs such as gemcitabine and paclitaxel, and can release them at the site of primary and metastatic neoplasms. The inhibitory effect of MSCs loaded with anti-cancer agents on the proliferation of cancer cells has also been observed. However, not all known chemotherapeutic agents can be used in this approach, mainly due to their cytotoxicity towards MSCs and insufficient loading and release capacity. Quinazoline derivatives appear to be an attractive choice for this therapeutic solution due to their biological and pharmacological properties. There are several quinazolines that have been approved for clinical use as anticancer drugs by the US Food and Drug Administration (FDA). It gives hope that the synthesis of new quinazoline derivatives and the development of methods of their application may contribute to the establishment of highly effective therapies for oncological patients. However, a deeper understanding of interactions between MSCs and tumor cells, and the exploration of the possibilities of using quinazoline derivatives in MSC-based therapy is necessary to achieve this goal. The aim of this review is to discuss the prospects for using MSC-based cell therapy in cancer treatment and the potential use of quinazolines in this procedure.     

Recent Advances in Biological Activity,New Formulations and Prodrugs of Ferulic Acid

Trans-ferulic acid (FA) is a derivative of 4-hydroxycinnamic acid, which is found in many food products, fruits and beverages. It has scientifically proven antioxidant, anti-inflammatory and antibacterial properties. However, its low ability to permeate through biological barriers (e.g., the blood–brain barrier, BBB), its low bioavailability and its fast elimination from the gastrointestinal tract after oral administration limit its clinical use, e.g., for the treatment of neurodegenerative diseases, such as Alzheimer’s disease. Therefore, new nanotechnological approaches are developed in order to regulate intracellular transport of ferulic acid. The objective of this review is to summarize the last decade’s research on biological properties of ferulic acid and innovative ways of its delivery, supporting pharmacological therapy.     

Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).     

A grasp‐based motion planning algorithm for character animation

The design of autonomous characters capable of planning their own motions continues to be a challenge for computer animation. We present a novel kinematic motion‐planning algorithm for character animation which addresses some of the outstanding problems. The problem domain for our algorithm is as follows: given a constrained environment with designated handholds and footholds, plan a motion through this space towards some desired goal. Our algorithm is based on a stochastic search procedure which is guided by a combination of geometric constraints, posture heuristics, and distance‐to‐goal metrics. The method provides a single framework for the use of multiple modes of locomotion in planning motions through these constrained, unstructured environments. We illustrate our results with demonstrations of a human character using walking, swinging, climbing, and crawling in order to navigate through various obstacle courses. Copyright © 2001 John Wiley & Sons, Ltd.     

Selected Applications of Chitosan Composites

Chitosan is one of the emerging materials for various applications. The most intensive studies have focused on its use as a biomaterial and for biomedical, cosmetic, and packaging systems. The research on biodegradable food packaging systems over conventional non-biodegradable packaging systems has gained much importance in the last decade. The deacetylation of chitin, a polysaccharide mainly obtained from crustaceans and shrimp shells, yields chitosan. The deacetylation process of chitin leads to the generation of primary amino groups. The functional activity of chitosan is generally owed to this amino group, which imparts inherent antioxidant and antimicrobial activity to the chitosan. Further, since chitosan is a naturally derived polymer, it is biodegradable and safe for human consumption. Food-focused researchers are exploiting the properties of chitosan to develop biodegradable food packaging systems. However, the properties of packaging systems using chitosan can be improved by adding different additives or blending chitosan with other polymers. In this review, we report on the different properties of chitosan that make it suitable for food packaging applications, various methods to develop chitosan-based packaging films, and finally, the applications of chitosan in developing multifunctional food packaging materials. Here we present a short overview of the chitosan-based nanocomposites, beginning with principal properties, selected preparation techniques, and finally, selected current research.     

Identification and determination of the glyceride and tris-(2-hydroxyethyl)isocyanurate structures in the average macromolecule of a polyester with carbon-13-NMR spectroscopy: Analysis of the polyester average structure

The ¹³C-NMR approach to quantitative analysis of a polyester resin synthesized from dimethylterephthalate, ethylene glycol, tris-(2-hydroxyethyl)isocyanurate (THEIC), and glycerol is presented. Various glyceride and isocyanurate structures formed during the esterification have been identified and analyzed, at first in simple model systems and then in the structure of the resin. The contents of particular structural units were determined as well as a hypothetical average macromolecule of the resin defined. The assignments of ¹³C-NMR signals were made and correlated with the ¹H shifts using a 2D-HETCOR experiment. © 1998 John Wiley & Sons, Inc. J. Appl. Polym. Sci. 70: 675–687, 1998     

Ostarine-Induced Myogenic Differentiation in C2C12, L6, and Rat Muscles

Ostarine (also known as enobosarm or Gtx-024) belongs to the selective androgen receptor modulators (SARMs). It is a substance with an aryl-propionamide structure, classified as a non-steroidal compound that is not subjected to the typical steroid transformations of aromatization and reduction by α5 reductase. Despite ongoing research on ostarine, knowledge about it is still limited. Earlier studies indicated that ostarine may affect the metabolism of muscle tissue, but this mechanism has not been yet described. We aimed to investigate the effect of ostarine on the differentiation and metabolism of muscle. Using C2C12 and L6 cells, as well as muscles obtained from rats administered ostarine, we showed that ostarine stimulates C2C12 and L6 proliferation and cell viability and that this effect is mediated by androgen receptor (AR) and ERK1/2 kinase activation (p < 0.01). We also found that ostarine stimulates muscle cell differentiation by increasing myogenin, MyoD, and MyH expression in both types of cells (p < 0.01). Moreover, pharmacological blocking of AR inhibits the stimulatory effect of ostarine. We further demonstrated that 30 days of ostarine administration increases myogenin, MyoD, and MyH expression, as well as muscle mass, in rats (p < 0.01). Based on our research, we conclude that ostarine stimulates muscle tissue proliferation and differentiation via the androgen receptor.     

Protein-Mediated Transformations of Superparamagnetic Nanoparticles Evidenced by Single-Particle Inductively Coupled Plasma Tandem Mass Spectrometry: A Disaggregation Phenomenon

Progress toward translating superparamagnetic iron oxide nanoparticles (SPIONs) with specific diagnostic and therapeutic properties for clinical applications depends on developing and implementing appropriate methodologies that would allow in-depth characterizations of their behavior in a real biological environment. Herein, we report a versatile approach for studying interactions between SPIONs and proteins using single-particle inductively coupled plasma tandem mass spectrometry. By monitoring the changes in the size distribution upon exposure to human serum, the formation of stable protein corona is revealed, accompanied by particle disaggregation.     

Porphyrin Based 2D-MOF Structures as Dual-Kinetic Sorafenib Nanocarriers for Hepatoma Treatment

The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.     

In Vitro and In Silico Kinetic Studies of Patented 1,7-diEthyl and 1,7-diMethyl Aminoalkanol Derivatives as New Inhibitors of Acetylcholinesterase

Two aminoalkanol derivatives of 1,7-diEthyl-8,9-diphenyl-4azatricyclo (5.2.1.02.6) dec-8-ene-3,5,10-trione and two derivatives of 1,7-diMethyl-8,9-diphenyl-4-azatricyclo (5.2.1.02.6) dec-8-ene-3,5,10-trione were evaluated in vitro for their inhibition efficacy of acetylcholinesterase. The Km, Vmax, slope angles of Lineweaver–Burk plots, Ki and IC₅₀ values showed that all four aminoalkanol derivatives are competitive inhibitors of acetylcholinesterase whose inhibitory potency depends, to a varying extent, on the nature of the four different substituents present in the main compound structure. Studies have shown that the most potent acetylcholinesterase inhibitors are derivatives containing isopropylamine and/or methyl substituents in their structure. In contrast, dimethylamine and/or ethyl substituents seem to have a weaker, albeit visible, effect on the inhibitory potency of acetylcholinesterase. Additionally, docking studies suggest that studied compounds binds with the peripheral anionic site and not enter into the catalytic pocket due to the presence of the sterically extended substituent.