Furthermore, the increased expression of MEPE we observed in the presence of p-ASARM both in the 3D culture model and in the wounded pulp rat model is consistent with previous publications reporting an upregulation of MEPE in osteoblasts of Hyp mice. Thus, in XLH, overexpressed MEPE in osteoblasts results in the potential for more ASARM peptide to accumulate in the ECM of bone and dentin, which would not be cleaved away as a result of the inactivating PHEX mutations. As the ASARM peptides are highly resistant to proteases and are only known to be degraded by PHEX, this positive-feedback loop on MEPE expression induced by ASARM peptides might exacerbate the disease and would thus be a mechanism contributing in part to the mineralization defect seen in XLH. Indeed, increased levels of ASARM peptide in serum have been reported in hypophosphatemic patients and in Hyp mice. Furthermore, the ASARM peptide has been shown to accumulate in the renal tubules of Hyp mice, and recent evidence suggests that it may directly impair phosphate uptake and LEE011 induce hypophosphatemia. Studies are currently in progress using pulp cells derived from XLH patients to better understand the function of PHEX in this complex pathologic process. In conclusion, using in vitro and in vivo models we demonstrate that the MEPE-derived ASARM peptide �C previously identified in XLH dentin �C inhibits both ECM mineralization and odontoblast differentiation, while increasing MEPE expression. These results provide for a partial mechanistic explanation of the pathogenesis of XLH whereby direct inhibition of mineralization by p-ASARM positively reinforced by increased MEPE expression induced by ASARM, together with decreased odontoblast differentiation to produce less dentin, leads to the mineralization defect and increased pulp chamber characteristic of teeth in XLH. Further studies are required to determine whether the MEPE-derived ASARM peptide affects odontoblast differentiation through indirect cell-signaling induced by defective ECM mineralization and/or by direct cell signaling with potential internalization of the peptide by cells. Collectively, these data appear promising in guiding the development of novel therapies for XLH through targeting the MEPE-ASARM system. Artemisinin-based combination therapy is currently the mainstay of malaria treatment in both children and adults, while in pregnancy it can be used only in the second and third trimester. Pregnant women are more susceptible to malaria infection than other adults, resulting in placental malaria and anaemia and increasing the risk of low birth weight and infant mortality. Approximately 50 million women living in malaria-endemic areas become pregnant each year, half of them in areas of SSA with stable malaria transmission. More recently, several studies have confirmed higher gametocyte carriage after SP compared to other antimalarial drugs, with peak gametocyte prevalence at around seven days posttreatment. However, gametocytes present in the peripheral blood after SP treatment seem to have low infectivity for Anopheles gambiae sensu stricto mosquitoes. A similar ABT-199 increase of gametocyte carriage after CTX treatment has been observed. CTX has similar mechanisms of action and resistance patterns to SP and therefore, concerns were raised on the potential impact of CTX resistance on SP efficacy.