Differential induction of apoptosis by type A and B trichothecenes in Jurkat T-lymphocytes.

Several studies have shown that the mycotoxins T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and nivalenol (NIV) affect lymphocyte functioning. However, the molecular mechanisms underlying the immunomodulatory effects of these trichothecenes are not defined yet. In this study, the potency of the type A trichothecenes T-2 toxin and DAS, and the type B trichothecenes DON (and its metabolite de-epoxy-deoxynivalenol; DOM-1) and NIV to reduce mitochondrial activity and to induce apoptosis of Jurkat T cells (human T lymphocytes) were examined. T-2 toxin and DAS are much more cytotoxic at low concentrations than DON and NIV as shown by the AlamarBlue cytotoxicity assay. In addition, the mechanism whereby DON and NIV induced cytotoxicity is mainly via apoptosis as we observed phosphatidylserine externalization, mitochondrial release of cytochrome c, procaspase-3 degradation and Bcl-2 degradation. In contrast, type A trichothecenes reduce the mitochondrial activity at approximately 1000-fold lower concentrations than the type B trichothecenes, resulting in necrosis. These data suggest that the mechanisms resulting in cytotoxic effects are different for type A and type B trichothecenes.     

Perspectives on next steps in classification of oro‐facial pain – Part 3: biomarkers of chronic oro‐facial pain – from research to clinic

The purpose of this study was to review the current status of biomarkers used in oro‐facial pain conditions. Specifically, we critically appraise their relative strengths and weaknesses for assessing mechanisms associated with the oro‐facial pain conditions and interpret that information in the light of their current value for use in diagnosis. In the third section, we explore biomarkers through the perspective of ontological realism. We discuss ontological problems of biomarkers as currently widely conceptualised and implemented. This leads to recommendations for research practice aimed to a better understanding of the potential contribution that biomarkers might make to oro‐facial pain diagnosis and thereby fulfil our goal for an expanded multidimensional framework for oro‐facial pain conditions that would include a third axis.     

Catalyst-free four-component domino synthetic approach toward versatile multicyclic spirooxindole pyran scaffolds

A new versatile strategy involving a sequential four-component reaction of the nitroketene dithioacetals, alkylamine/benzylamine, isatin and various enolizable active methylene structures (pyrazolone, barbituric acid, 1,3-indandione and 2-hydroxy-1,4-naphthoquinone) as precursors under mild and catalyst-free conditions results in the synthesis of new functionalized spirooxindole pyrans named spiro[indoline-3,4′-pyrano[2,3-c]pyrazol], spiro[indoline-3,5′-pyrano[2,3-d]pyrimidine], spiro[indeno[1,2-b]pyran-4,3′-indoline] and spiro[benzo[g]chromene-4,3′-indoline] in moderate to good yields. The use of various active methylene compounds affords a range of skeletally distinct spirooxindole-based heterocycles with potential biological properties. The present strategy has many advantages, such as convenient one-pot operation, simple workup procedures and straightforward isolation without using tedious purification steps such as column chromatography, progress under catalyst-free condition and high molecular diversity.

Synthesis of spirooxindole pyrans by a sequential four-component reaction of nitroketene dithioacetals, alkylamine/benzylamine, isatin, and active methylene compounds.     

Zinc(ii) triazole meso-arylsubstituted porphyrins for UV-visible chloride and bromide detection. Adsorption and catalytic degradation of malachite green dye

Three new triazole meso-arylporphyrins (4a–c) were synthesized by the copper(i)-catalyzed azide alkyne cycloaddition (CuAAC) “click” reaction in high yield. The corresponding zinc(ii) coordination compounds (5a–c) have also been prepared. All 4a–c and 5a–c porphyrin species were fully characterized by elemental analysis, electrospray ionization and MALDI-TOF mass spectrometry, infrared spectroscopy, proton nuclear magnetic resonance, UV-visible, fluorescence and cyclic voltammetry. The zinc(ii) 5a–c complexes have been tested as detectors for Cl⁻ and Br⁻ anions. UV-visible titrations reveal that these host systems exhibit strong anion binding affinities. The efficiency of the adsorption of the malachite green dye (MG) dye on the 4a–c free base porphyrins and the corresponding zinc(ii) complexes 5a–c was investigated by a kinetic study using these synthetic porphyrin derivatives as adsorbents. The use of our triazole Zn(ii) complexes in the catalytic degradation of the MG dye is the first example where a metalloporphyrin is involved in the MG dye decolorization reaction. The degradation reactions were carried out using an ecological oxidant (H₂O₂), where the efficiency of the decolorization has been characterized by UV-visible spectroscopic analysis. Several factors affecting the degradation phenomenon have been studied. The energetic parameters concerning the degradation process have also been determined.

Three triazole porphyrins and there corresponding zinc complexes are described as well as their spectroscopic and electrochemical data. The chloride and bromide sensing efficiency and the degradation of the malachite green dye are also reported.