The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.     

Chemosensitization of U-87 MG Glioblastoma Cells by Neobavaisoflavone towards Doxorubicin and Etoposide

Glioblastoma (GB) is the most common type of glioma, which is distinguished by high mortality. Due to the rapid progression of the tumor and drug resistance, the treatment is often ineffective. The development of novel therapies in a big part concerns the application of anti-cancer agents already used in clinical practice, unfortunately often with limited effects. This could be overcome through the use of compounds that possess chemosensitizing properties. In our previous work, it has been shown that neobavaisoflavone (NBIF) enhances the in vitro activity of doxorubicin in GB cells. The aim of this study was a further investigation of the possible chemosensitizing effects of this isoflavone. The experimental panel involving image cytometry techniques, such as count assay, examination of mitochondrial membrane potential, Annexin V assay, and cell cycle analysis, was performed in human glioblastoma U-87 MG cells and normal human astrocytes (NHA) treated with NBIF, doxorubicin, etoposide, and their mixes with NBIF. NBIF in co-treatment with etoposide or doxorubicin caused an increase in the population of apoptotic cells and prompted alterations in the cell cycle. NBIF enhances the pro-apoptotic activity of etoposide and doxorubicin in U-87 MG cells, which could be a sign of the chemosensitizing properties of the isoflavone.     

Digitally Alloyed Modulated Precursor Flow Epitaxial Growth of Ternary AlGaN with Binary AlN and GaN Sub-Layers and Observation of Compositional Inhomogeneity

We report the growth of ternary aluminum gallium nitride (AlGaN) layers on AlN/sapphire template/substrates by digitally alloyed modulated precursor flow epitaxial growth (DA-MPEG), which combined an MPEG AlN sub-layer with a conventional metalorganic chemical vapor deposition (MOCVD)-grown GaN sub-layer. The overall composition in DA-MPEG Al _x Ga_1−x N was controlled by adjustment of the growth time (i.e., the thickness) of the GaN sub-layer. As the GaN sub-layer growth time increased, the Al composition in AlGaN decreased to 50%, but the surface morphology of the AlGaN layer became rough, and a three-dimensional structure with islands appeared for the DA-MPEG AlGaN with relatively thick GaN sub-layers, possibly resulting from the Ga adatom surface migration behavior and/or the strain built up from lattice mismatch between AlN and GaN sub-layers with increasing GaN sub-layer growth time. Through strain analysis by high-resolution x-ray diffraction, reciprocal space mapping, and scanning transmission electron microscopy, it was found that there was compositional inhomogeneity in the DA-MPEG AlGaN with AlN and GaN binary sub-layers for the case of the layer with relatively thick GaN sub-layers.     

Hydrogen peroxide sensing with horseradish peroxidase-modified polymer single conical nanochannels

Inspired from the funtioning and responsiveness of biological ion channels, researchers attempt to develop biosensing systems based on polymer and solid-state nanochannels. The applicability of these nanochannels for detection/sensing of any foreign analyte in the surrounding environment depends critically on the surface characteristics of the inner walls. Attaching recognition sites to the channel walls leads to the preparation of sensors targeted at a specific molecule. There are many nanochannel platforms for the detection of DNA and proteins, but only a few are capable of detecting small molecules. Here, we describe a nanochannel platform for the detection of hydrogen peroxide, H(2)O(2), which is not only a toxic waste product in the cellular systems but also a key player in the redox signaling pathways. The sensor is based on single conical nanochannels fabricated in an ion tracked polymer membrane. The inner walls of the channel are decorated with horseradish peroxidase (HRP) enzyme using carbodiimide coupling chemistry. The success of the HRP immobilization on the channel surface is confirmed by measuring the pH-dependent current-voltage (I-V) curves of the system. The reported HRP-nanochannel system detects nanomolar concentrations of H(2)O(2) with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) as the substrate. The immobilized HRP enzyme is thus capable of inducing redox reactions in a subfemtoliter volume of single nanochannels. We demonstrate that functioning of the designed biosensor is reversible and can be used multiple times to detect H(2)O(2) at various concentrations.     

The possible use of alkali metal modified NbMCM-41 in the synthesis of 1,4-dihydropyridine intermediates

In this work we have prepared the catalysts containing all alkali metals (from Li to Cs) supported on mesoporous niobosilicate molecular sieve, NbMCM-41, and for comparison also loaded on silicate MCM-41. The materials were characterised by N₂ adsorption, XRD, and test reactions (acetonylacetone cyclisation and Knoevenagel condensation). It has been found that niobium located in the mesoporous material plays a role of structural promoter which prevents the solid from the disordering caused by the treatment with alkali metal solution. Moreover, it changes the catalytic properties of basic centres generated by alkali metal loading in relation to those observed for alkali metals supported on silicate MCM-41. Rb/NbMCM-41 has been proposed as active and selective catalyst in the condensation of benzaldehyde and different substituted benzaldehydes with ethyl acetoacetate towards the synthesis of intermediates in the preparation of some dihydropyridines.     

Study of a new resin-based composites containing hydroxyapatite filler using Raman and infrared spectroscopy

The degree of conversion of polymeric matrix in hydroxyapatite-containing dental fillings by Raman and infrared spectroscopy has been determined. Resin-based dental composites are one of the most popular filling materials used in dentistry. These light-cured materials are characterized by the value of the degree of conversion, which depends on curing time and influences the quality of obtained dental filling. Distribution of the filler into polymeric matrix, which has a significant impact on the properties of the final product, has been determined by Raman mapping. The applied procedure also has allowed to present the changes of the degree of conversion on the examined surfaces. The results of the study demonstrate the versatility of the Raman spectroscopy as the analytical spectroscopic technique for determining chemical properties of dental fillings and providing insight into their organization at the microstructural level. The obtained degree of conversion values have been compared with data for the commercially available dental fillings characterized by other authors.     

Ionic liquids as performance additives for water‐based printing inks

For the first time, the use of ionic liquids as additives for printing inks in order to improve the wettability of the printing base by the ink is presented. The aim of this work was to study the influence of ionic liquids on the selected properties of water‐based printing ink and the prints. The contact angles of the printing inks on the printing base were measured. Modified flexographic inks were laboratory printed on polypropylene plastic film. The impact of small amounts of various ionic liquids on printing ink colour was examined in terms of the optical density of the full‐tone area, the colour parameters (L*, a*, b*, CIE), the total colour difference, and the gloss of the dried ink film. The influence of ionic liquids on the ink contact angle, the optical density, and the L*a*b* coordinates is discussed. In general, the investigated ionic liquids improve the wettability of water‐based flexographic printing ink, with an acceptable total colour difference. The optical density is increased for printing inks containing ionic liquids in comparison with the original flexographic printing ink, Process.     

Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease. In many cases, HCC is an effect of chronic liver inflammation, which leads to the formation of a complex tumor microenvironment (TME) composed of immune and stromal cells. The TME of HCC patients is a challenge for therapies, as it is involved in metastasis and the development of resistance. However, given that the TME is an intricate system of immune and stromal cells interacting with cancer cells, new immune-based therapies are being developed to target the TME of HCC. Therefore, understanding the complexity of the TME in HCC will provide new possibilities to design novel and more effective immunotherapeutics and combinatorial therapies to overcome resistance to treatment. In this review, we describe the role of inflammation during the development and progression of HCC by focusing on TME. We also describe the most recent therapeutic advances for HCC and possible combinatorial treatment options.     

European consumers’ use of and trust in information sources about fish

This paper focuses on identifying segments of consumers based on their use of and trust in information sources about fish. Cross-sectional data were collected through the SEAFOODplus pan-European consumer survey (n = 4786) with samples representative for age and region in Belgium, the Netherlands, Denmark, Spain and Poland. Three distinct clusters, based on use of and trust in fish information sources, were identified: Sceptic (24.0%), Enthusiast (41.4%) and Confident (34.6%). Those consumer segments differed significantly with respect to use of and interest in information cues on fish labels, knowledge and behaviour towards fish, and socio-demographic profile. Recommendations for the use of multiple sources targeted to a particular audience’s interest and behavioural profile were formulated.     

Immunomodulatory Drugs in the Treatment of Hidradenitis Suppurativa—Possibilities and Limitations

Hidradenitis suppurativa, also known as acne inversa, is a chronic, progressive, debilitating, recurrent inflammatory skin disease characterized by the occurrence of very severe, persistent, painful nodules, abscesses, and fistulas, most commonly found in the skin folds of the axilla, groin, gluteal, and perianal areas. Treatment is rather difficult and typically requires the use of multiple modalities. Regardless of the presence of several therapeutic options, treatment often turns out to be ineffective or poorly selected concerning the clinical picture of the disease. Thus, the search for new biologics and other target treatments of hidradenitis suppurativa is ongoing. The safety and efficacy of adalimumab, still the only U.S. Food and Drug Administration approved biologic in the hidradenitis suppurativa treatment, paved the way for new drugs to be compared with it. Several more drugs with new immunological targets are currently under investigation for the treatment of acne inversa. The aim of the article was to present the current and future targets of acne inversa treatment, simultaneously providing insights into the molecular pathomechanisms of the disease.