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Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC = 10-19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a C-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2.

The oxidation kinetics of lignosulfonates (LS) from acidic magnesium-based sulfite pulping of Eucalyptus globulus wood with oxygen under alkaline conditions was studied. The analysis of oxidation products in the reaction system O 2 /NaOH revealed a predominance of aromatic aldehydes (vanillin and syringic aldehyde) though small amounts of vanillic and syringic acids and acetophenone/phenylacetaldehyde derivatives have also been detected. The rate constant of syringic aldehyde formation was roughly twice of that for vanillin. The effective activation energies for the oxidation of LS to aromatic aldehydes (ca. 60-70 kJ/mol) were rather different to those found for the formation of aromatic acids (ca. 110 kJ/mol) indicating different mechanisms involved in the rate-determining reaction step. The addition of catalyst (copper salt, 20% w/w) promoted the LS oxidation with increments of aromatic aldehyde yields by 25-50%. The maximum yields of syringic aldehyde and vanillin upon LS oxidation were 16.1 and 4.5%, respectively (150°C, 20 min, P O 2 ) 10 bar, 0.9 M NaOH solution). The highly negative effect of concomitant sugars in sulfite liquor to the yield of aromatic aldehydes was highlighted.

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The purpose of this paper is to describe a case of juvenile cystic adenomyoma in a 17 year-old female patient with severe dysmenorrhoea unresponsive to non-steroidal anti-inflammatory drugs. The patient presents progressively worsening dysmenorrhoea that started 2 years after menarche and a cystic uterine lesion in MRI. The cyclic nature of symptoms, the similarity of the lesion and endometrium in MRI signal intensity and response to hormone suppression are consistent with juvenile cystic adenomyoma. The treatment depends on the age of the patient, severity of her symptoms and size and localisation of the cyst. This is a rare condition in young nulliparous women with a challenging differential diagnosis. This case highlights the relevance of MRI in the patient's study, featuring important characteristics of the lesion that disclosed the final diagnosis.

Vitis vinifera, one of the most cultivated fruit crops, is susceptible to several diseases particularly caused by fungus and oomycete pathogens. In contrast, other Vitis species (American, Asian) display different degrees of tolerance/resistance to these pathogens, being widely used in breeding programs to introgress resistance traits in elite V. vinifera cultivars. Secondary metabolites are important players in plant defence responses. Therefore, the characterization of the metabolic profiles associated with disease resistance and susceptibility traits in grapevine is a promising approach to identify trait-related biomarkers. In this work, the leaf metabolic composition of eleven Vitis genotypes was analysed using an untargeted metabolomics approach. A total of 190 putative metabolites were found to discriminate resistant/partial resistant from susceptible genotypes. The biological relevance of discriminative compounds was assessed by pathway analysis. Several compounds were selected as promising biomarkers and the expression of genes coding for enzymes associated with their metabolic pathways was analysed. Reference genes for these grapevine genotypes were established for normalisation of candidate gene expression. The leucoanthocyanidin reductase 2 gene (LAR2) presented a significant increase of expression in susceptible genotypes, in accordance with catechin accumulation in this analysis group. Up to our knowledge this is the first time that metabolic constitutive biomarkers are proposed, opening new insights into plant selection on breeding programs.

Graphical abstractImproved and efficient metabolite extraction method for maximizing the number of metabolites identified from a single biological sample, compatible with DI-FTICR-MS-based metabolomics.

V. vinifera ‘Pinot noir’ leaves have a high content of biologically active phytochemical compounds of interest for pharmaceutical and food industries.