ABSTRACT
The milk fat globule membrane (MFGM) appears to play an important role in infant neurocognitive development; however, its mechanism(s) of action remains unclear. This study aimed to investigate the role of a dietary MFGM supplement on the lipid profiles of different neonatal brain regions. Ten-day-old male piglets (4−5 kg) were fed unsupplemented infant formula (control, n = 7) or an infant formula supplemented with low (4%) or high (8%) levels of MFGM (n = 8 each) daily for 21 days. Piglets were then euthanized, and brain tissues were sectioned. Untargeted liquid chromatography-mass spectrometry lipidomics was performed on the cerebellum, hippocampus, prefrontal cortex, and the rest of the brain. The analyses identified 271 and 171 lipids using positive and negative ionization modes, respectively, spanning 16 different lipid classes. MFGM consumption did not significantly alter the lipidome in most brain regions, regardless of dose, compared to the control infant formula. However, 16 triacylglyceride species were increased in the hippocampus (t-test, p-value < 0.05) of the high-supplemented piglets. Most lipids (262 (96.7%) and 160 (93.6%), respectively) differed significantly between different brain regions (ANOVA, false discovery rate corrected p-value < 0.05) independent of diet. Thus, this study highlighted that dietary MFGM altered lipid abundance in the hippocampus and detected large differences in lipid profiles between neonatal piglet brain regions.
ABSTRACT
The fungal metabolite TAN-2483B has a 2,6-trans-relationship across the pyran ring of its furo[3,4-b]pyran-5-one core, which has thwarted previous attempts at its synthesis. We have now developed a chiral pool approach to this core and prepared side-chain analogues of TAN-2483B. The synthesis relies on ring expansion of a reactive furan ring-fused dibromocyclopropane and alkynylation of the resulting pyran. The furan ring is constructed by palladium-catalysed carbonylative lactonisation. Various side-chains are appended through Wittig-type chemistry. The prepared analogues showed micromolar activity towards cancer cell lines HL-60, 1A9 and MCF-7 and certain human disease-relevant kinases, including Bruton's tyrosine kinase (Btk).
Subject(s)
Antineoplastic Agents/chemical synthesis , Lactones/chemistry , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Pyrans/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Lactones/chemical synthesis , Lactones/pharmacology , Molecular Structure , Phosphotransferases/antagonists & inhibitors , Phosphotransferases/metabolism , Protein Kinase Inhibitors/pharmacology , Pyrans/chemical synthesis , Pyrans/pharmacology , Structure-Activity RelationshipABSTRACT
The reductions in the transmission of emission originating from a fluorophore dissolved in a polymer matrix due to light scattering were compared in two forms of planar waveguides used as luminescent solar concentrators: a thin film of poly(methylmethacrylate) (PMMA) spin-coated on a glass plate and a solid PMMA plate of the same dimensions. The losses attributable to light scattering encountered in the waveguide consisting of the thin film of polymer coated on a glass plate were not detectable within experimental uncertainty, whereas the losses in the solid polymer plate were significant. The losses in the solid plate are interpreted as arising from light-scattering centers comprising minute bubbles of vapor/gas, incomplete polymerization or water clusters that are introduced during or after the thermally induced polymerization process.