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.     

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.     

Quantitative Measurement of Propellant Stabilizers with tlc and liquid-crystalline method of visualization

Basic compounds of propellants, nitrate esters decompose forming nitrogen oxides as the catalytic products. To inhibit further decomposition, stabilizer reacts with nitrogen oxides, and finally non-catalytic products are formed, so autocatalytic decomposition is minimized. In this way, chemical stability of propellant increases, but the content of stabilizer decreases. In this paper, the possibility of quantitative analysis of the weight loss of propellant stabilizer using the TLC method and the liquid crystal method of visualization is presented. The advantages of solid phase extraction (SPE) application in such analysis are also shown.     

Multifunctional porous membranes with antibacterial properties

Abstract

The paper describes the results of research on obtaining porous membranes produced from polylactide fibers (PLA) by electrospinning, additionally modified with gentamicin antibiotic (GM) at the stage of preparing a spinning solution to provide bactericidal properties. Both solid (1^oPNF) and porous (2^oPNF 3^oPNF) polymer fibers were obtained, and the control of fiber porosity was achieved using various solvent systems: dichloromethane (DCM), dimethylformamide (DMF), chloroform (CHL) and dimethyl sulfoxide (DMSO). Three types of fibers differing in morphology (fiber diameter) and mean pore size were obtained. Physicochemical properties of porous and solid drug-containing fibers were examined, determining their surface free energy (SFE) and wetting angle (CA), and the effectiveness of modification with the drug was confirmed in spectroscopic studies (FTIR-ATR). Antibacterial activity of the prepared drug-modified nonwovens was confirmed by the disk diffusion method against Gram-negative Escherichia coli bacteria strain. The results of tests have shown that depending on the type of solvents used at the electrospinning stage, porous fibers can be obtained from polylactide. The addition of gentamicin affected antibacterial properties, and the pore size determined the rate of drug release monitored by the ion coupled plasma method (ICP).     

Evolution of viscoelastic behaviour of a curing LY5052 epoxy resin in the rubbery state

In this work, we investigate the relationship between the rubbery modulus and the degree of cure for partially to fully cured LY5052 epoxy resin. In particular, this paper experimentally tests an existing model formulated for shear modulus by redefining for in the tensile storage modulus. Experiments to characterize viscoelastic behaviour were performed in a dynamic mechanical and thermal analysis (DMTA) instrument in the frequency domain. Master curves are then created from DMTA using general time–temperature–cure superposition. The master curves are then normalized using the model so that the master curve does not depend on the properties in the rubbery region. This results in a unique master curve that describes the viscoelastic behaviour of the LY5052 epoxy resin for the given conditions. Once the relationship between the rubbery modulus and the degree of cure has been established, the amount of experimental characterization can be reduced. This could lead to the development of simplified experimental methodologies and simplified models to characterize the viscoelasticity of low molecular weight resins like the LY5052 epoxy resin system.     

Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders

We recently reported the presence of various cyclopropane fatty acids—among them, cyclopropaneoctanoic acid 2‐hexyl—in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2‐hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2‐hexyl was determined by gas chromatography–mass spectrometry (GC–MS) in non‐obese controls, obese patients, obese patients after a 3‐month low‐calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2‐hexyl than controls. Switching obese individuals to a low‐calorie (low‐lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2‐hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2‐hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia‐related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2‐hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI.