Investigation of the Associations of Novel Inflammatory Biomarkers—Systemic Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI)—With the Severity of Coronary Artery Disease and Acute Coronary Syndrome Occurrence

Atherosclerosis, the underlying cause of coronary artery disease (CAD), has a significant inflammatory component. White blood cell count is an affordable and accessible way to assess the systemic immune response, as it comprises many subgroups with distinct and complex functions. Considering their multidirectional effect on atherosclerosis, new biomarkers integrating various leukocyte subgroups, the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response Index (SIRI), were recently devised to describe the balance between inflammation and immune reaction. This research aimed to evaluate the relationship of the intensity of inflammation measured by these biomarkers with the severity of CAD assessed with coronary angiography and with the diagnosis of acute coronary syndrome (ACS) or stable CAD in 699 patients. SIRI, but not SII, was associated with the diagnosis, having the highest values for patients with ACS (STEMI), significantly higher than in patients with stable CAD (p < 0.01). The highest SII and SIRI values were observed in patients with three-vessel CAD. SII and SIRI require further in-depth and well-designed research to evaluate their potential in a clinical setting.     

The Influence of Angiotensin Peptides on Survival and Motility of Human High-Grade Serous Ovarian Cancer Cells in Serum Starvation Conditions

High-grade serous ovarian carcinoma (HGSOC) is the most frequent and malignant form of ovarian cancer. A local renin–angiotensin system (RAS) has been found in the ovary, and changes in selected components of this system were observed in pathological states and also in ovarian cancer. In the present study, we examined the effect of three peptides, Ang-(1-7), Ang-(1-9) and Ang-(3-7), on proliferation and motility of the OVPA8 cell line, a new well-defined and preclinical model of HGSOC. We confirmed the presence of mRNA for all angiotensin receptors in the tested cells. Furthermore, our findings indicate that all tested angiotensin peptides increased the metabolic serum in the medium by activation of cell defense mechanisms such as nuclear factor kappaB signaling pathway andapoptosis. Moreover, tested angiotensin peptides intensified serum starvation-induced cell cycle arrest at the G0/G1 phase. In the case of Ang-(3-7), a significant decrease in the number of Ki67 positive cells (Ki67+) and reduced percentage of activated ERK1/2 levels in ovarian cancer cells were additionally reported. The angiotensin-induced effect of the accumulation of cells in the G0/G1 phase was not observed in OVPA8 cells growing on the medium with 10% FBS. Moreover, in the case of Ang-(3-7), the tendency was quite the opposite. Ang-(1-7) but not Ang-(1-9) or Ang-(3-7) increased the mobility of reluctant-to-migrate OVAP8 cells cultured in the serum-free medium. In any cases, the changes in the expression of VIM and HIF1A gene, associated with epithelial–mesenchymal transition (EMT), were not observed. In conclusion, we speculate that the adaptation to starvation in nutrient-deprived tumors can be modulated by peptides from the renin–angiotensin system. The influence of angiotensin peptides on cancer cells is highly dependent on the availability of growth factors and nutrients.     

Controlling the Spatiotemporal Release of Nerve Growth Factor by Chitosan/Polycaprolactone Conduits for Use in Peripheral Nerve Regeneration

Tubular polymeric structures have been recognized in the treatment of peripheral nerves as comparable to autologous grafting. The best therapeutic outcomes are obtained with conduits releasing therapeutic molecules. In this study, a new approach for the incorporation of biologically active agent-loaded microspheres into the structure of chitosan/polycaprolactone conduits was developed. The support of a polycaprolactone helix formed by 3D melt extrusion was coated with dopamine in order to adsorb nerve growth factor-loaded microspheres. The complex analysis of the influence of process factors on the coverage efficiency of polycaprolactone helix by nerve grow factor-loaded microspheres was analyzed. Thus, the PCL helix characterized with the highest adsorption of microspheres was subjected to nerve growth factor release studies, and finally incorporated into chitosan hydrogel deposit through the process of electrophoretic deposition. It was demonstrated by chemical and physical tests that the chitosan/polycaprolactone conduit meets the requirements imposed on peripheral nerve implants, particularly mimicking mechanical properties of surrounding soft tissue. Moreover, the conduit may support regrowing nerves for a prolonged period, as its structure and integrity persist upon incubation in lysozyme-contained PBS solution up to 28 days at body temperature. In vitro cytocompatibility toward mHippoE-18 embryonic hippocampal cells of the chitosan/polycaprolactone conduit was proven. Most importantly, the developed conduits stimulate axonal growth and support monocyte activation, the latter is advantageous especially at early stages of nerve regeneration. It was demonstrated that, through the described approach for controlling spatiotemporal release of nerve growth factors, these biocompatible structures adjusted to the specific peripheral nerve injury case can be manufactured.     

Neonatal Rat Glia Cultured in Physiological Normoxia for Modeling Neuropathological Conditions In Vitro

Cell culture conditions were proven to highly affect crucial biological processes like proliferation, differentiation, intercellular crosstalk, and senescence. Oxygen tension is one of the major factors influencing cell metabolism and thus, modulating cellular response to pathophysiological conditions. In this context, the presented study aimed at the development of a protocol for efficient culture of rat neonatal glial cells (microglia, astrocytes, and oligodendrocytes) in oxygen concentrations relevant to the nervous tissue. The protocol allows for obtaining three major cell populations, which play crucial roles in sustaining tissue homeostasis and are known to be activated in response to a wide spectrum of external stimuli. The cells are cultured in media without supplement addition to avoid potential modulation of cell processes. The application of active biomolecules for coating culturing surfaces might be useful for mirroring physiological cell interactions with extracellular matrix components. The cell fractions can be assembled as cocultures to further evaluate investigated mechanisms, intercellular crosstalk, or cell response to tested pharmacological compounds. Applying additional procedures, like transient oxygen and glucose deprivation, allows to mimic in vitro the selected pathophysiological conditions. The presented culture system for neonatal rat glial cells is a highly useful tool for in vitro modeling selected neuropathological conditions.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.     

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.     

Microwave- and ultrasound-assisted convective drying of raspberries: Drying kinetics and microstructural changes

The drying kinetics, microstructural alteration, and rehydration properties of raspberry samples were studied experimentally in this work. Five different drying programs with the application of microwaves (MW) and ultrasound (US) were used, including convective drying (CV) as a reference test. The drying experiments were performed using a hybrid chamber dryer equipped with airborne ultrasound and microwave generators. The modified Page model was successfully used to describe the drying kinetics of raspberry fruits. Next, microstructural properties (porosity and total pore volume) of the dried samples were determined from the postprocessing of the images which were acquired using a lab-scale X-ray microtomograph. The results show a significantly shorter drying time by 54–64% for CVUS, 69% for CVMW, and 79% for CVMWUS; and a lower energy consumption resulting in energy saving of 14–23% for CVUS, 54% for CVMW, and 59% for CVMWUS as compared to CV. It is also shown that the average drying rate of raspberry samples increases by maximum fourfold with the application of both ultrasound and microwave radiations in CV. In addition, a higher porosity, total pore volume, and a better rehydration property were found for the raspberry samples dried with US than with MW assistance.     

Mechanical properties and thermal stability of tungsten boride films deposited by radio frequency magnetron sputtering

Tungsten and boron compounds belong to the group of superhard materials since their hardness could exceed 40?GPa. In this study, the properties of the tungsten boride WB_x coatings deposited by radio frequency magnetron sputtering were investigated. The sputtering was performed from specially prepared targets that were composed of boron and tungsten mixed in a molar ratio of 2.5 and sintered in Spark Plasma Sintering (SPS) process. WB films were deposited on silicon (100) and stainless steel 304 substrates at temperatures of 23 ÷ 770?°C. Microstructure, chemical and phase composition were investigated by using Scanning Electron Microscope (SEM), X-Ray Photoelectron Spectroscopy (XPS) and X-Ray Diffraction (XRD), respectively. The mechanical properties like Vickers hardness and Young's modulus were obtained by using nanoindentation test at a load of 5 ÷ 100 mN. The friction coefficient and wear resistance of αWB coatings were investigated in scratch test and reciprocal sliding wear instrumentation. Moreover, in order to investigate thermal properties, the αWB films were annealed at 1000?°C in argon/air for 1?h and at 250?°C for 2?h in air atmosphere. Results of our research confirm that αWB coatings can be considered as an alternative to superhard materials in the production of wear resistant, long-lasting tools.     

Visualization of particles arrangement during filling stage of polyamide 6 – metal insert injection molding

An isotactic polypropylene filled with talc and mica particles was used for visualization of molten polymer flow lines during filling of mold cavity with metal insert. The talc particles orientation in polypropylene matrix was followed by scanning electron microscopy. For the quantification of platelet particles orientation in molten polymer flow localized near metal wall, the Herman's function was applied. An existence of regions with well oriented, randomly organized talc particles depending on the shape and cross‐section of the channels, was found and reported. The domain with the most disorganized platelet particles was detected in the region where polymer streamed around the sharp corner of the metal insert. Such a kind of disarranged region could be the weakest part of the whole injection molded polymeric element. POLYM. ENG. SCI., 59:E271–E278, 2019. © 2019 Society of Plastics Engineers