Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.     

gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway

Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.     

Synthesis, Molecular Characterization and Preliminary Antioxidant Activity Evaluation of Quercetin Fatty Esters

Quercetin shows interesting pharmacological effects, but its use in topical applications is limited by its low skin permeability and solubility. In this work, the synthesis of highly lipophilic quercetin esters with oleic, linoleic and linolenic acid useful as topical quercetin prodrugs is reported. Partial OH esterification is advisable to maintain the antioxidant activity of these compounds; tetraesters and triesters can be achieved by modulating the reaction conditions utilized for the total esterification of quercetin. The chemical structures of the esters were proven by spectroscopic techniques; quantum chemical NMR calculation were mandatory to unequivocally assign the free position in triesters. Finally, the antioxidant activity of all the synthesized compounds was determined by the 2,2-diphenyl-1-picryl-hydrazyl method and by 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) assay.     

Potenziale und Grenzen der Sekundärrohstoffgewinnung – Ergebnisse der r4-Begleitforschung

The socio-economic and ecological impacts of selected projects of the BMBF funding program “r⁴ – Innovative Technologies for Resource Efficiency – Research for the Provision of Raw Materials of Strategic Economic Importance” are presented. Many, but not all, research projects indicate a potential improvement of the supply situation in Germany. In some cases, the provision of secondary raw materials is unprofitable or ecologically detrimental. These cases require a balancing between security of supply and other economic and ecological objectives.     

Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs

A convenient synthesis of imatinib, a potent inhibitor of ABL1 kinase and widely prescribed drug for the treatment of a variety of leukemias, was devised and applied to the construction of a series of novel imatinib analogues featuring a number of non‐aromatic structural motifs in place of the parent molecule's phenyl moiety. These analogues were subsequently evaluated for their biopharmaceutical properties (e.g., ABL1 kinase inhibitory activity, cytotoxicity). The bicyclo[1.1.1]pentane‐ and cubane‐containing analogues were found to possess higher themodynamic solubility, whereas cubane‐ and cyclohexyl‐containing analogues exhibited the highest inhibitory activity against ABL1 kinase and the most potent cytotoxicity values against cancer cell lines K562 and SUP‐B15. Molecular modeling was employed to rationalize the weak activity of the compounds against ABL1 kinase, and it is likely that the observed cytotoxicity of these agents arises through off‐target effects.     

Photopolymerizable multifunctional monomers and their evaluation as reactive Bis‐GMA eluents

Bis‐GMA {2,2‐bis[4‐(2′‐hydroxy‐3′‐methacryloyloxy‐propoxy)‐phenyl]‐propane}, TEGDMA <2‐{2‐[2‐(2‐methylprop‐2‐enoyloxy)ethoxy]ethoxy}ethyl‐2‐methylprop‐2‐enoate>, and methyl methacrylate (MMA) are some of the most commonly used monomers in the field of restorative dentistry. These compounds are characterized by having one or two terminal double bonds. Besides the effort to synthesize new monomers, several problems still affect the clinical behavior of contemporary dental materials. In this work, two monomers with three terminal double bonds, 5A13DA and 5A13DMA, were synthesized. Both monomers were used to completely replace TEGDMA as reactive diluent of photopolymerizable dental resin composites containing Bis‐GMA. The effects of 5A13DA and 5A13DMA on flexural properties, double bond conversion, water sorption, solubility, and polymerization shrinkage were evaluated. In addition, both monomers were evaluated as crosslinking agents for methylmethacrylate, resulting in copolymers with enhanced thermal stability. The results obtained suggest that newly synthesized monomers are potential substitutes for TEGDMA in the formulation of dental composites, providing 50% lower volumetric shrinkage than the composite resin used as control and adequate mechanical properties. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46240.     

Influence of ionic liquid composition on the stability of polyvinyl chloride‐based ionic liquid inclusion membranes in aqueous solution

Membrane technology has gained significant importance with the incorporation of ionic liquids into their structure. This work shows the influence of ionic liquid composition on the stability of PVC‐based polymer ionic liquid inclusion membranes (PILIMs) in aqueous solution. Among the ILs investigated, those membranes which contain between 20 and 30%_w/w of the least soluble, [OMIM⁺][PF₆^?] and [OMIM⁺][Ntf₂^?], exhibit losses of IL lower than 10%. For both ILs, the amount immobilized was maximum for the membranes with 30%_w/w of IL (0.0838 and 0.0832 g, respectively). On the contrary, the ionic liquid loss increases as its solubility in water increase, reaching 99.52% when PILIMs are prepared with 70%_w/w of [OMIM⁺][BF₄^?]. The results demonstrate that the stability of PILIMs depends on the solubility of the IL in the surrounding phase and the specific interaction between the IL and the polymeric support for PVC‐to‐IL ratios higher than 30%_w/w. © 2016 American Institute of Chemical Engineers AIChE J, 63: 770–780, 2017     

Effect of the drying process on the compressive strength and cell proliferation of hydroxyapatite‐derived scaffolds

The compressive strength and MC3T3 cell proliferation response of robocast hydroxyapatite‐derived scaffolds was evaluated for samples fabricated by conventional and freeze‐drying methods followed by sintering at 1100 or 1300°C. Both the sintering temperature and, especially, the drying method affected significantly the size and morphology of the residual microporosity within the robocast scaffold's struts. The freeze‐drying method generated a persistent large (1‐10 μm) microporosity of dendritic morphology that was found to improve the biological response of hydroxyapatite‐derived scaffolds. Conversely, conventional drying enhances the compressive strength of the structures. Strength was also increased at the higher sintering temperature, although at the expense of a poorer cell proliferation behavior. The results of this study suggest that the use of a freeze drying process after printing by robocasting provides a very appropriate method for enhancing the biological performance and reliability of bioceramic robocast scaffolds without severely reducing their compressive strength. And, thus, shows promise as an effective method to optimize the performance of robocast scaffolds for bone tissue regeneration.     

Design,Synthesis, and Biological Evaluation of Levoglucosenone‐Derived Ras Activation Inhibitors

A panel of new potential Ras ligands was generated by decorating a tricyclic levoglucosenone‐derived scaffold with aromatic moieties. Some members of the panel show in vitro inhibitory activity toward the nucleotide exchange process on Ras and are toxic to some human cancer cell lines.

     

The influence of carbon particle type in fly ashes on mercury adsorption

Recent research has shown that certain fly ash materials produced in coal combustion for power generation have an affinity for the mercury compounds present in flue gases. However, the exact nature of Hg-fly ash interactions is still unknown and the different variables that influence mercury adsorption need to be identified. In this work the microscopic components of fly ashes derived from the combustion of different types of feed blends of different coal rank and mercury adsorption were investigated. The aim of this research was to establish relationships between Hg retention and the type of unburned carbons present in various fly ashes. The fly ashes and fly ash fractions studied were used as sorbent beds for high mercury concentrations, conditions in which mercury retention is highly favored. From the results obtained it was confirmed that the role of the unburned carbon components in mercury capture may depend, among other factors, on the type of unburned carbon. Fly ashes capture different species of mercury depending on their nature and the type of anisotropic particles.