Effects of biomaterials for Lab-on-a-chip production on cell growth and expression of differentiated functions of leukemic cell lines

The rapid increase of the applications for Lab-on-a-chip devices has attracted the interest of researchers and engineers on standard process of the electronics industry for low production costs and large scale development, necessary for disposable applications. The printed circuit board technology could be used for this purpose, in particular for the wide range of materials available. In this paper, assays on biocompatibility of materials used for Lab-on-a-chip fabrication has been carried out using two tumor cell lines growing in suspension, the human chronic myelogenous leukemia K562 cell line, able to undergo erythroid differentiation when cultured with chemical inducers, and the lymphoblastoid cell line (LCL), extensively used for screening of cytotoxic T-lymphocytes (CTLs). We have demonstrated that some materials strongly inhibit cell proliferation of both the two cell lines to an extent higher that 70–75%, but only after a prolonged exposure of 3–6 days (Copper, Gold over Nickel, Aramid fiber filled epoxy uncured, b-stage epoxy die attach film, Tesa 4985 adhesive tape, Pyralux uncured, Copper + 1-octodecanethiol). However, when experiments were performed with short incubation time (1 h), only Aramid fiber filled epoxy uncured was cytotoxic. Variation of the results concerning the other materials was appreciable when the experiments performed on two cell lines were compared together. Furthermore, the effects of the materials on erythroid differentiation and CTL-mediated LCL lysis confirmed, in most of the cases, the data obtained in cytotoxic and antiproliferative tests.     

Bemessungsrelevante Kennwerte von Feinbeton für einaxiale Druckbeanspruchung

Design Parameters of Fine Grained Concrete for Uniaxial Compressive Loading Textile reinforced concrete (TRC) allows the design of thin‐structured concrete elements with a high load‐bearing capacity. The mechanical properties and stress‐strain relations under shortterm compressive loading of so called fine grained binder systems which are used as matrix are presented in this paper. The application of known mathematical formulations (e. g. simplified parabola‐rectangle stress‐strain curves for dimensioning purposes, prediction models for characteristic creep parameters) is investigated and design values of fine grained concrete are proposed.     

Identifying contemporary and historic sources of soil polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in an industrial urban setting

A study of soil polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) concentrations was undertaken in the vicinity of a municipal solid waste incinerator (MSWI) in Newcastle upon Tyne as a result of concerns raised by local residents about potential contamination from fugitive and stack emissions. The study area was divided into four sectors (north-east (NE), south-east (SE), north-west (NW) and south-west (SW)) around the MSWI, and sampling sites were located up to a distance of 2.25 km. Based on air dispersion modelling, the sampling density was four times greater in the NE (downwind) sector compared to the SW (upwind) direction, and twice as great in the NW and SE sectors. PCDD/F concentrations found in soil samples ranged from 6 to 1911 ng I-TEQ/kg DW with a median of 32 ng I-TEQ/kg DW. There was no evidence of elevated concentrations downwind of the MSWI compared to other directions, nor of any trend in concentration at increasing distance from the MSWI. We concluded, therefore, that the MSWI fugitive and stack emissions were not a major source of PCDD/F contamination. Analysis of PCDD/F homologue profiles showed that samples exhibiting furan-dominated and OCDD-dominated profiles and a profile characteristic of the MSWI ash occurred in distinct clusters. Those samples showing the furan-dominated profile had the largest PCDD/F concentrations measured as I-TEQ, followed by samples with the incinerator profile, the deposition profile, and the OCDD-dominated profile. We identified some contamination hotspots located in the SW and SE sampling sectors (upwind of the MSWI), and potential sources for these hotspots were sought by using historic land use data from maps of the locality dating back to 1856. We concluded that the cluster of very high concentrations of PCDD/F in soils showing the furan homologue profile were most likely to have resulted from the disposal of graphite electrode sludges from brine electrolysis carried out at a chemical works between the 1890s and the 1930s.     

Coupling AFM,DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit^® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm² h), and even the pH of the sample with Eudragit^® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.     

The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis

Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the role of glycosaminoglycans (GAGs) as potential co-receptors in the process of CCL26-induced eosinophil chemotaxis. For this purpose, we have first identified the GAG-binding site of CCL26 by a site-directed mutagenesis approach in the form of an alanine screening. A panel of GAG-binding-deficient mutants has been designed, generated, and analyzed with respect to their binding affinities to heparan sulphate (HS) by isothermal fluorescence titration studies. This showed that basic amino acids in the α-helical part of CCL26 are strongly involved in GAG-binding. In chemotaxis experiments, we found that decreased GAG-binding affinity correlated with decreased chemotactic activity, which indicates an involvement of GAGs in eosinophil migration. This was further proven by the negative impact of heparinase III treatment and, independently, by the incubation of eosinophils with an anti heparan sulfate antibody. We finally investigated eosinophils’ proteoglycan (PG) expression patterns by real-time PCR, which revealed the highest expression level for serglycin. Including an anti-serglycin antibody in CCL26-induced eosinophil migration experiments reduced the chemotaxis of these immune cells, thereby proving the dependence of eosinophil mobilization on the proteoglycan serglycin.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea

We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with K_i in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with K_i in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.     

Circular RNAs in Pregnancy and the Placenta

The emerging field of circular RNAs (circRNAs) has identified their novel roles in the development and function of many cancers and inspired the interest of many researchers. circRNAs are also found throughout the healthy body, as well as in other pathological states, but while research into the function and abundance of circRNAs has progressed, our overall understanding of these molecules remains primitive. Importantly, recent studies are elucidating new roles for circRNAs in pregnancy, particularly in the placenta. Given that many of the genes responsible for circRNA production in cancer are also highly expressed in the placenta, it is likely that the same genes act in the production of circRNAs in the placenta. Furthermore, placental development can be referred to as ‘controlled cancer’, as it shares many key signalling pathways and hallmarks with tumour growth and metastasis. Hence, the roles of circRNAs in this field are important to study with respect to pregnancy success but also may provide novel insights for cancer progression. This review illuminates the known roles of circRNAs in pregnancy and the placenta, as well as demonstrating differential placental expressions of circRNAs between complicated and uncomplicated pregnancies.