Ken Ng

Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.

This mini-review provides a general understanding of electrospray ionisation mass spectrometry (ESI-MS) which has become an increasingly important technique in the clinical laboratory for structural study or quantitative measurement of metabolites in a complex biological sample. The first part of the review explains the electrospray ionisation process, design of mass spectrometers with separation capability, characteristics of the mass spectrum, and practical considerations in quantitative analysis. The second part then focuses on some clinical applications. The capability of ESI-tandem-MS in measuring bio-molecules sharing similar molecular structures makes it particularly useful in screening for inborn errors of amino acid, fatty acid, purine, pyrimidine metabolism and diagnosis of galactosaemia and peroxisomal disorders. Electrospray ionisation is also efficient in generating cluster ions for structural elucidation of macromolecules. This has fostered a new and improved approach (vs electrophoresis) for identification and quantification of haemoglobin variants. With the understanding of glycohaemoglobin structure, an IFCC reference method for glycohaemoglobin assay has been established using ESI-MS. It represents a significant advancement for the standardisation of HbA1c in diabetic monitoring. With its other applications such as in therapeutic drug monitoring, ESI-MS will continue to exert an important influence in the future development and organisation of the clinical laboratory service.

The gut microbiota plays a prominent role in human health. Alterations in the gut microbiota are linked to the development of chronic diseases such as obesity, inflammatory bowel disease, metabolic syndrome, and certain cancers. We know that diet plays an important role to initiate, shape, and modulate the gut microbiota. Long-term dietary patterns are shown to be closely related with the gut microbiota enterotypes, specifically long-term consumption of carbohydrates (related to Prevotella abundance) or a diet rich in protein and animal fats (correlated to Bacteroides). Short-term consumption of solely animal- or plant-based diets have rapid and reproducible modulatory effects on the human gut microbiota. These alterations in microbiota profile by dietary alterations can be due to impact of different dietary macronutrients, carbohydrates, protein, and fat, which have diverse modulatory effects on gut microbial composition. Food-derived phenolics, which encompass structural variants of flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, coumarins, stilbenes, ellagitannins, and lignans can modify the gut microbiota. Gut microbes have been shown to act on dietary fibers and phenolics to produce functional metabolites that contribute to gut health. Here, we discuss recent studies on the impacts of phenolics and phenolic fiber-rich foods on the human gut microbiota and provide an insight into potential synergistic roles between their bacterial metabolic products in the regulation of the intestinal microbiota.