Impedance analysis of a phosphatidylcholine-phosphatidylethanolamine system in bilayer lipid membranes

Electrochemical impedance spectroscopy was used for the study of two-component lipid membranes. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were to be investigated, because of their presence in biological membranes. Capacitance values of pure components are 0.62 and 0.32 μF cm⁻², respectively. The 1:1 complex was formed during formation of the PC-PE lipid membrane. Formation of the complex can explain the deviation from the additivity rule. This equilibrium was described by mathematical equations and was further verified experimentally. Adequate equations let us calculate such parameters as: capacitance of the complex molecule, area occupied by the complex molecule as well as the stability constant of the complex.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

Carbon fibers modified with carbon nanotubes

Carbon nanotubes were used to modify a polyacrylonitrile (PAN) polymer solution before the manufacture of the carbon fiber precursor. The modified PAN fibers were spun from a dimethylformamide solution containing a small amount of single-walled carbon nanotubes. The fibers were characterized by thermogravimetry and optical and scanning electron microscopy. Structure, morphology, and selected properties of the composite polymeric fibers and the fibers after carbonization are characterized. The mechanical properties of the fibers are examined. It is found that nanotubes in the PAN solution have a strong tendency to form agglomerates that inhibit suitable macromolecular chain orientation of the carbon fiber precursor. Fibers manufactured from such a solution have similar mechanical properties to those from a pure PAN precursor, and after carbonization the resultant carbon fibers are very weak. A comparison of pure carbon fibers and those containing nanotubes reveals slight differences in their structural ordering.     

Compendium on Food Crop Plants as a Platform for Pharmaceutical Protein Production

Tremendous advances in crop biotechnology related to the availability of molecular tools and methods developed for transformation and regeneration of specific plant species have been observed. As a consequence, the interest in plant molecular farming aimed at producing the desired therapeutic proteins has significantly increased. Since the middle of the 1980s, recombinant pharmaceuticals have transformed the treatment of many serious diseases and nowadays are used in all branches of medicine. The available systems of the synthesis include wild-type or modified mammalian cells, plants or plant cell cultures, insects, yeast, fungi, or bacteria. Undeniable benefits such as well-characterised breeding conditions, safety, and relatively low costs of production make plants an attractive yet competitive platform for biopharmaceutical production. Some of the vegetable plants that have edible tubers, fruits, leaves, or seeds may be desirable as inexpensive bioreactors because these organs can provide edible vaccines and thus omit the purification step of the final product. Some crucial facts in the development of plant-made pharmaceuticals are presented here in brief. Although crop systems do not require more strictly dedicated optimization of methodologies at any stages of the of biopharmaceutical production process, here we recall the complete framework of such a project, along with theoretical background. Thus, a brief review of the advantages and disadvantages of different systems, the principles for the selection of cis elements for the expression cassettes, and available methods of plant transformation, through to the protein recovery and purification stage, are all presented here. We also outline the achievements in the production of biopharmaceuticals in economically important crop plants and provide examples of their clinical trials and commercialization.     

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.     

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.     

Study on the new bone cement based on calcium sulfate and Mg,CO3 doped hydroxyapatite

In order to improve some features of bone substitutes the new self-setting composite-type implant material based on Mg²⁺/CO₃^2? co-substituted hydroxyapatite (Mg-CHA) and calcium sulfate hemihydrate (CSH) was developed. Synthetic hydroxyapatites doped with small amounts of additives found in natural bone (e.g. Mg²⁺ and CO₃^2?) are regarded as promising components of calcium phosphate bone cements (CPCs). The CPCs, now available on the market, due to low resorption rate are too stable to permit material degradation and are slowly replaced by the newly formed bone. To improve cement resorption we used calcium sulfate which is a well-known biodegradable and biocompatible bone defect filler. Combining properties of Mg-CHA and CSH allowed developing a new, promising, easy shapeable implant material with high potential for bone regeneration.