Synthesis and proteomic activity evaluation of a new isotope-coded affinity tagging (ICAT) reagent.

During recent years, quantitative proteome profiling has taken advantage of incorporating the traditional stable isotope dilution analysis into global scale or discovery-based proteomic experiments that use mass spectrometers as detectors to allow the pairwise study of differently expressed proteins. Quantitative protein analysis by means of the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS) enables the pairwise comparison of protein expression levels in biological samples. Herein, a modified ICAT reagent, named BAAICAT (beta-alanine-arm-ICAT) in which the polyether linker is replaced by a more water-soluble polyamide one, was investigated

N-Substituted l-Iminosugars for the Treatment of Sanfilippo Type B Syndrome

: Sanfilippo syndrome comprises a group of four genetic diseases due to the lack or decreased activity of enzymes involved in heparan sulfate (HS) catabolism. HS accumulation in lysosomes and other cellular compartments results in tissue and organ dysfunctions, leading to a wide range of clinical symptoms including severe neurodegeneration. To date, no approved treatments for Sanfilippo disease exist. Here, we report the ability of N-substituted l-iminosugars to significantly reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and in a neuronal cellular model of Sanfilippo B subtype. Particularly, we found that they increase the levels of defective α-N-acetylglucosaminidase and correct its proper sorting toward the lysosomal compartment. Furthermore, l-iminosugars reduce HS accumulation by downregulating protein levels of exostosin glycosyltransferases. These results highlight an interesting pharmacological potential of these glycomimetics in Sanfilippo syndrome, paving the way for the development of novel therapeutic approaches for the treatment of such incurable disease

SARS-CoV-2 in myelodysplastic syndromes: a snapshot from early Italian experience

Myelodysplastic syndrome patients are subjects of advanced age, vulnerable and frail, whose outcome is heavily influenced by pre-existing comorbidities worsening the hematologic condition. Infections are a rather common cause of death (around 30%), especially, but not only, for IPSS-R higher risk patients.1–3 In MDS there is a significant impairment of lymphopoiesis, resulting in lymphopenia (ALC<1.0109 /l) in around 38% of MDS patients and poor prognosis.4 Data on innate and adoptive immune systems (either disease related or due to immunosenescence) and the subsequent supposed susceptibility and incidence of viral infections in MDS are scarce.