Expression of the Selected Proteins of JAK/STAT Signaling Pathway in Diseases with Oral Mucosa Involvement

The JAK/STAT signal pathway is a system of intracellular proteins used by many cytokines and growth factors to express genes responsible for the process of cell activation, proliferation and differentiation. There has been numerous inflammatory and autoimmune diseases identified where the JAK/STAT signaling is disrupted; however, there are only a few papers concerning autoimmune bullous diseases published. The aim of this study was to evaluate the expression of proteins: JAK3, STAT2, STAT4 and STAT6 in epithelium lesions in patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), oral lichen planus (LP) and chronic ulcerative stomatitis (CUS), as well as in the control group. Immunohistochemistry and immunoblotting were used to evaluate expression of selected proteins. We found significantly higher expression of selected JAK/STAT proteins in oral mucosa lesions in study groups in comparison to the control group, which indicates participation of JAK/STAT pathway in pathogenesis of these diseases. In BP and PV there were no increased STAT2 expression, whereas in CUS and LP no increased STAT4 expression occurred. The differences in expression of JAK/STAT proteins in selected disorders have been observed. These results create new potential therapeutic targets for the treatment.     

Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe,Ru)

The quest to find new inhibitors of biologically relevant targets is considered an important strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC₅₀. Metallocarbonyl derivatives, in general, did not show significant inhibition activity against these enzymes, the most potent inhibitor was the (aminomethyl)benzylphosphonate 8a (IC₅₀ = 1.215 µM against AChE). Molecular docking analysis of AChE and (aminomethyl)benzylphosphonates 8a–c showed the strongest interactions of 8a and AChE compared to isomers 8b and 8c. Cytotoxicity studies of synthesized compounds towards the V79 cell line were also performed and discussed.     

Inhibition of Atherosclerosis and Liver Steatosis by Agmatine in Western Diet-Fed apoE-Knockout Mice Is Associated with Decrease in Hepatic De Novo Lipogenesis and Reduction in Plasma Triglyceride/High-Density Lipoprotein Cholesterol Ratio

Atherosclerosis and NAFLD are the leading causes of death worldwide. The hallmark of NAFLD is triglyceride accumulation caused by an imbalance between lipogenesis de novo and fatty acid oxidation. Agmatine, an endogenous metabolite of arginine, exerts a protective effect on mitochondria and can modulate fatty acid metabolism. In the present study, we investigate the influence of agmatine on the progression of atherosclerotic lesions and the development of hepatic steatosis in apoE^−/− mice fed with a Western high-fat diet, with a particular focus on its effects on the DNL pathway in the liver. We have proved that treatment of agmatine inhibits the progression of atherosclerosis and attenuates hepatic steatosis in apoE^−/− mice on a Western diet. Such effects are associated with decreased total macrophage content in atherosclerotic plaque as well as a decrease in the TG levels and the TG/HDL ratio in plasma. Agmatine also reduced TG accumulation in the liver and decreased the expression of hepatic genes and proteins involved in lipogenesis de novo such as SREBP-1c, FASN and SCD1. In conclusion, agmatine may present therapeutic potential for the treatment of atherosclerosis and fatty liver disease. However, an exact understanding of the mechanisms of the advantageous actions of agmatine requires further study.     

Failure of Immunotherapy—The Molecular and Immunological Origin of Immunotherapy Resistance in Lung Cancer

Immune checkpoint inhibitors (ICIs) have a huge impact on clinical treatment results in non-small cell lung cancer (NSCLC). Blocking antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death protein ligand 1 (PD-L1) or CTLA-4 (cytotoxic T cell antigen 4) have been developed and approved for the treatment of NSCLC patients. However, a large number of patients develop resistance to this type of treatment. Primary and secondary immunotherapy resistance are distinguished. No solid biomarkers are available that are appropriate to predict the unique sensitivity to immunotherapy. Knowledge of predictive markers involved in treatment resistance is fundamental for planning of new treatment combinations. Scientists focused research on the use of immunotherapy as an essential treatment in combination with other therapy strategies, which could increase cancer immunogenicity by generating tumor cells death and new antigen release as well as by targeting other immune checkpoints and tumor microenvironment. In the present review, we summarize the current knowledge of molecular bases underlying immunotherapy resistance and discuss the capabilities and the reason of different therapeutic combinations.     

Hiding in Plain Sight: Cuticular Compound Profile Matching Conceals a Larval Tortoise Beetle in its Host Chemical Cloud

Larvae of tortoise beetles are postulated to have fecal shields as the main defensive strategy against predators. Such a device protects beetles both physically and chemically. In order to examine how larvae Chelymorpha reimoseri are protected against predatory ants, which frequently visit extrafloral nectaries in their host plant, the morning glory Ipomoea carnea, we conducted anti-predation bioassays with live 5th instars. In the field, larvae in contact with ants had survival between 40 and 73 %, independently of shield presence. In the laboratory, when exposed to Camponotus crassus, larvae with shields had significantly higher survival (85 %) than those without shields (64 %). In both scenarios, larval survival was significantly higher when compared with palatable Spodoptera frugiperda larvae, as the latter were all consumed. We also observed that when C. reimoseri larvae showed no movement, the ants walked on them without attacking. We hypothesized that if the larval integument has a pattern of cuticular compounds (CCs) similar to that of its host plant, larvae would be rendered chemically camouflaged. In the field and laboratory, the freeze-dried palatable larvae of S. frugiperda treated with CCs of 5th instar C. reimoseri and left on I. carnea leaves were significantly less removed by ants than controls without these compounds. We also found a similarity of approximately 50 % between the CCs in C. reimoseri larvae and I. carnea host leaves. Both findings provide evidence in support of the hypothesis that chemical camouflage plays an important role in larval defense, which is reported for the first time in an ectophagous leaf beetle larva.     

Application of the Basalt Powder as a Filler for Polypropylene Composites With Improved Thermo‐Mechanical Stability and Reduced Flammability

The influence of the basalt powder (BP) on mechanical properties as well as on thermal stability and flammability of the isotactic polypropylene (iPP) composites was investigated. Thermo‐mechanical stability of the pure polypropylene and composite materials containing from 5 up to 40 wt% BP was defined in static and dynamic testing conditions with the use of the heat distortion temperature measurement, vicat softening point temperature test, and dynamic mechanical thermal analysis. All measurements showed, unequivocally, a significant improvement of thermo‐mechanical stability of the composite materials which was directly related to an increasing amount of inorganic filler. A research conducted on the mechanical properties revealed that stiffness and hardness of polypropylene‐based composites was affected by the addition of the filler, leading to a strong increase of both mechanical parameters. Moreover, the application of thermogravimetric analysis and cone calorimetry measurements allowed to determine the composites with highest thermal stability, which was dependent on the concentration of the filler. Changes observed in the polypropylene‐based composites properties were related to an increase of thermal diffusivity caused by presence of the BP measured by modified Angstrom method. POLYM. ENG. SCI., 59:E71–E79, 2019. © 2018 Society of Plastics Engineers     

Influence of Sedimentation of Atoms on Structural and Thermoelectric Properties of Bi-Sb Alloys

Functionally graded thermoelectric materials (FGTMs) have been prepared by sedimentation of atoms under a strong gravitational field. Starting samples of Bi _x Sb_1?x alloys with different composition x were synthesized by melting of metals and subsequent annealing of quenched samples. The thermoelectric properties (Seebeck coefficient, electrical conductivity) of the starting materials were characterized over the temperature range from 300 K to 525 K. Strong gravity experiments were performed in a unique ultracentrifuge apparatus under acceleration of over 0.5 × 10⁶ G at temperatures of 538 K and 623 K. Changes of the microstructure and chemical composition were analyzed using scanning electron microscopy with energy-dispersive x-ray spectroscopy analysis. The distribution of the Seebeck coefficient of the Bi-Sb alloys was characterized by scanning thermoelectric microprobe. As a result of sedimentation, large changes in chemical composition (x = 0.45 to 1) were obtained. It was found that the changes in chemical composition were correlated with alterations of the Seebeck coefficient. The obtained experimental data allowed the development of a semiempirical model for the selection of optimal processing parameters for preparation of Bi-Sb alloys with required thermoelectric properties.