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A Treatment for Sickle Cell Disease

Author(s): Aiden Johnson and Selena Brown

SCD is a severe systemic disease with few treatment options for disease-related consequences. The disease's hallmark is microvascular vaso-occlusion, which causes significant morbidity and mortality. Vaso-occlusion is at the root of a complex pattern of difficulties associated with the hyper-adhesiveness of circulating blood cells and endothelium. The activation of numerous adhesion receptor/ligand pairs downstream of P-selectin overexpression initiates the vaso-occlusive cascade. By preventing these sticky contacts, blocking P-selectin has been demonstrated to successfully prevent vaso-occlusion. However, the efficacy of the E-selectin inhibitor uproleselan in Acute Myeloid Leukaemia (AML) patients may prompt the development of comparable medicines that target selectinligand sticky interactions to reduce the clinical implications of vaso-occlusion. The glycan (carbohydrate) determinant for selectin binding was discovered to be the sialylated and fucosylated tetrasaccharide sialyl Lewis(X) (sLeX). As a result, new synthetic lectins that target glycan determinants on P-selectin-ligands may prove to be more specific and effective medications, not only for preventing but also for treating patients with Vasoocclusion Crises (VOCs).