Focus: Allergic Diseases and Type II Immunity: Amlexanox: A Novel Therapeutic for Atopic,Metabolic, and Inflammatory Disease

Amlexanox, a small molecule targeted therapy which has been used in the treatment of atopic conditions was previously but is not currently available in the United States. Amlexanox has also been legally utilized and administered in Japan as a treatment for asthma, a chronic pulmonary disease characterized by inflammation of the lower respiratory tract. Amlexanox’s immune modulatory effects have been the subject of studies which have repurposed the drug for potential therapeutic applications in metabolic and inflammatory disease. Because amlexanox inhibits TANK-binding kinase1 (TBK1) and nuclear factor kB kinase epsilon (IKKε), several studies have demonstrated its usefulness through its evidence downregulation of the immune system and attenuation of downstream TBK1 signaling. Novel therapies, such as amlexanox, for inflammatory conditions such as asthma will continue to be of value in clinical management. This report summarizes key applications of the drug based on animal and human studies and explores its potential in treatment of metabolic and inflammatory diseases.     

Small Molecule Metabolite Extraction Strategy for Improving LC/MS Detection of Cancer Cell Metabolome

Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system. “Oncometabolomics” is a rapidly emerging field with potential for developing specific biomarkers for early detection, diagnosis, and disease prognosis. Given the power of this technology, the availability of standardized sample preparation methods for immortalized human cancer cell lines is critical toward augmenting research in this direction. Using MCF-7 cells as a model system, we describe an approach for intracellular metabolite extraction from cell cultures for reproducible and comprehensive metabolite extraction. The samples, when injected onto a reverse-phase 50 × 2.1 mm Acquity 1.7-μm C18 column, using an ultra performance liquid chromatography system (UPLC) coupled with electrospray ionization-quadrupole-time-of-flight-mass spectrometry (ESI-Q-TOF-MS) in positive and negative modes, yielded a data matrix with a total of 2600 features. This method, when compared with a water-extraction procedure described earlier, was found to yield significantly higher coverage and detection of molecular features. Finally, we successfully tested the performance of this method for an array of human cancer cell lines used widely in the cancer research field.     

Use and Misuse of Material Transfer Agreements: Lessons in Proportionality from Research,Repositories, and Litigation

Material transfer agreements exist to facilitate the exchange of materials and associated data between researchers as well as to protect the interests of the researchers and their institutions. But this dual mandate can be a source of frustration for researchers, creating administrative burdens and slowing down collaborations. We argue here that in most cases in pre-competitive research, a simple agreement would suffice; the more complex agreements and mechanisms for their negotiation should be reserved for cases where the risks posed to the institution and the potential commercial value of the research reagents is high.     

The interaction of N-trifluoroacetylgalactosamine and its derivatives with winged bean (Psophocarpus tetragonolobus) basic agglutinin reveals differential mechanism of their recognition: a fluorine-19 nuclear magnetic resonance study

Here, we show the binding results of a leguminosae lectin, winged bean basic agglutinin (WBA I) to N-trifluoroacetylgalactosamine (NTFAGalN), methyl-α-N-trifluoroacetylgalactosamine (MeαNTFAGalN) and methyl-β-tifluoroacetylgalactosamine (MeβNTFAGalN) using ¹⁹?F NMR spectroscopy. No chemical shift difference between the free and bound states for NTFAGalN and MeβNTFAGalN, and 0.01-ppm chemical shift change for MeαNTFAGalN, demonstrate that the MeαNTFAGalN has a sufficiently long residence time on the protein binding site as compared to MeβNTFAGalN and the free anomers of NTFAGalN. The sugar anomers were found in slow exchange with the binding site of agglutinin. Consequently, we obtained their binding parameters to the protein using line shape analyses. Aforementioned analyses of the activation parameters for the interactions of these saccharides indicate that the binding of α and β anomers of NTFAGalN and MeαNTFAGalN is controlled enthalpically, while that of MeβNTFAGalN is controlled entropically. This asserts the sterically constrained nature of the interaction of the MeβNTFAGalN with WBA I. These studies thus highlight a significant role of the conformation of the monosaccharide ligands for their recognition by WBA I.