RESUMO
Oxazines are an important class of compounds in oxazine ligands and medical chemistry. Here, we describe a linear-selective allylation of imines with allyl electrophiles via cross-electrophile coupling reactions, followed by cyclization with halogenated reagents, providing a new strategy to afford oxazine compounds with a tetrasubstituted carbon center. Mechanistic studies indicate that α-amino carbanion, generated by successive single-electron transfer processes, is a key intermediate for nucleophile attack on π-allylpalladium in photoredox/palladium catalysis.
RESUMO
Accumulation of advanced glycation end products (AGEs) contributes to ageing and age-related diseases, especially type 2 diabetes. The NLRP3 inflammasome, as a vital component of the innate immune system, is implicated in the pathogenesis of type 2 diabetes. However, the role of the NLRP3 inflammasome in AGE-induced pancreatic islet damage remains largely unclear. Results showed that administration of AGEs (120 mg/kg for 6 weeks) in C57BL/6J mice induced an abnormal response to glucose (as measured by glucose tolerance and insulin release), pancreatic ß-cell ultrastructural lesion, and cell death. These effects were associated with an excessive superoxide anion level, significant increased protein expression levels for NADPH oxidase 2 (NOX2), thioredoxin-interacting protein (TXNIP), NLRP3, and cleaved IL-1ß, enhanced caspase-1 activity, and a significant increase in the levels of TXNIP-NLRP3 protein interaction. Ablation of the NLRP3 inflammasome or treatment with antioxidant N-acetyl-cysteine (NAC) clearly ameliorated these effects. In conclusion, our results reveal a possible mechanism for AGE-induced pancreatic islet damage upon NLRP3 inflammasome activation.
Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Inflamassomos/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Produtos Finais de Glicação Avançada/farmacologia , Humanos , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
OBJECTIVE: Establishing a subjective and objective method to conform the weighted coefficient in multicriteria optimization of the extraction technology about Chinese traditional compound drugs. METHOD: This article used analytic hierarchy process (AHP) to conform the weighted coefficient. RESULT: Consistency checking result (CR < 0.1) indicated that the weighted coefficient is reasonable and efficient. CONCLUSION: AHP method is simple and of high accuracy. This method improved on the scientific and accuracy of multicriteria optimization of the extraction technology about Chinese traditional compound drugs.