Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

Untersuchungen zur Tautomerie von o,o'-Dihydroxy-azofarbstoffen der Eriochrom-Reihe

Investigations on the Tautomerism of o,o'-Dihydroxy Azo Dyes of the Eriochrome Type Investigation of the u.v.-vis-, ¹H- and ¹³C-n.m.r. spectra of the title substances and the isomers 3 and 3p at different pH-values and in different solvent mixtures as well as of O,O'-dimethyl derivatives of 2 and 3 show that in aqueous solution as well the monoanions as the trianions exist in the azo forms only. The dianions exist in dependence on the solvents as mixtures of tautomers. The results of PPP calculations for different prototropic structures are in good accordance with the experimental results.     

Quantenchemische Untersuchungen zur Molekül- und Elektronenstruktur einfacher Azomethinimine und verwandter Verbindungen

Quantum Chemical Investigations of the Molecular and Electronic Structure of Simple Azomethine Imines and Related Compounds The molecular and electronic structure of simple azomethinimines are investigated by means of MINDO/3 and CNDO/2 calculations. The calculated molecular geometry is compared with X-ray results obtained for these compounds. Except for the NN-bond lengths MINDO/3 satisfactorily describes the molecular structure of azomethinimine and related π-electronic systems. The charges at the atoms along the conjugated chain are alternating as in polymethines. The terminal carbon atom carries a negative charge. This charge brings about an appreciable shielding of this carbon atom such as found in the ¹³C-n.m.r. spectrum. This result does not contradict a stabilization of azomethinimines in the crystal via = CH…︁OC interactions.     

Strategien zum Schließen der Stoffkreisläufe beim Recycling von Fluorpolymeren

In fluoropolymers, a large portion or even all of the hydrogen atoms in a polymer chain are replaced by fluorine, which results in a number of special properties such as high chemical and temperature resistance. As a result of this combination of properties, these high-performance polymers are not replaceable, or only with difficulty, for some applications. The recycling of polymers and the associated closing of material loops is an essential development task for the entire polymer industry. Materials such as fluoropolymers have a special position due to their chemical composition and their low market volume, as they cannot be recycled together with other bulk polymers at the end of their life cycle. This paper discusses different processes in terms of their technical maturity and suitability to allow fluoropolymers to be fully recycled.     

Electrochemical production of nanopore arrays in a nickel aluminium alloy

Directional solidification of a eutectic is a novel route for the production of nanostructures. This method was applied to the quasibinary NiAl-Re system. Re as the minor phase forms fibers, which are parallel aligned in the NiAl matrix. At a temperature of 1690 ± 10 °C using a thermal gradient of 40 °C cm⁻¹ and a growth rate of 30 mm h⁻¹, the fibers formed had a diameter of about 400 nm. An electrochemical method is presented here that simultaneously passivates the NiAl matrix and selectively electrodissolves the Re. In this manner, it was possible to form an array of nanopores each with the same diameter of 400 nm. The mechanisms behind this procedure, as well as the potential of this method for the production of nanoelectrode arrays or nanofilters are discussed.     

A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors

In this study, we synthesized and evaluated a new spirocyclic piperidine derivative 3 , containing a 4‐fluorobutyl side chain, as a PET radioligand for neuroimaging of σ₁ receptors. In vitro, compound 3 displayed high affinity for σ₁ receptors (K_i=1.2 nM ) as well as high selectivity. [¹⁸F] 3 radiosynthesis was performed from the corresponding tosylate precursor, with high radiochemical yield (45–51 %), purity (>98 %), and specific activity (>201 GBq μmol^?1). Metabolic stability of [¹⁸F] 3 in the brain of CD‐1 mice was verified, and no penetration of peripheral radiometabolites into the cerebral tissue was observed. Results of ex vivo autoradiography revealed that the distribution of [¹⁸F] 3 in the brain corresponded to regions with high σ₁ receptor density. The highest region‐specific total‐to‐nonspecific ratio was determined in the facial nucleus (4.00). Biodistribution studies indicated rapid and high levels in brain uptake of [¹⁸F] 3 (2.2 % ID per gram at 5 min p.i.). Pre‐administration of haloperidol significantly inhibited [¹⁸F] 3 uptake into the brain and σ₁ receptor‐expressing organs, further confirming in vivo target specificity.     

Electro-dissolution of 30Nb–Ti alloys in methanolic sulfuric acid—Optimal conditions for electropolishing

The electro-dissolution behaviour of a (30 at.%) Niobium–Titanium (NbTi) alloy in non-aqueous methanolic sulfuric acid solution using the rotating disc electrode (RDE) was ascertained. The optimal condition for electropolishing and the mechanism were proposed. The influence of the rotation rate, process temperature and sulfuric acid concentration on the dissolution kinetics was investigated. The dissolution rate (limiting current) increases linearly with increase in rotation rate and follows a Levich behaviour confirming a mass transport controlled process. The temperature dependence in terms of Arrhenius plot renders an activation energy value of E_a = 16.1 kJ mol⁻¹ for the process. The dissolution rate shows a strong dependence on the sulfuric acid concentration (1 M, 3 M and 5 M). Higher sulfuric acid concentrations lead to decreased dissolution rates (limiting current). The dissolution process is mass transport controlled in all concentrations of sulfuric acid. From an electrochemical perspective, a 3 M sulfuric acid was chosen as optimum owing to better controllability of the material removal rate. The dissolving ions are the probable rate limiting species, indicating a compact salt-film mechanism. The average root mean square (RMS) roughness value for an electropolished surface was approximately 10 nm, which is significantly lower than a mechanically polished surface.