Ricerc@Sapienza

Introduction CD28 is a crucial costimulatory receptor necessary for full T cell activation. One important contribution of CD28 to T cell activation relies on its ability to regulate T cell metabolism by enhancing nutrient uptake, aerobic glycolysis and anabolic pathways. Indeed, CD28 binds class 1A PI3K that in turn recruits and activates the PDK1/Akt/mTOR pathway. We have recently found that CD28 stimulation strongly up-regulates the expression of cytokines related to the Th17 cell phenotype in relapsing-remitting multiple sclerosis (RRMS) patients.

Sirtuins are NAD+-dependent deacylases that play crucial roles in the regulation of cellular metabolism, and as a result, are implicated in several diseases. The mitochondrial sirtuin Sirt4, for a long time considered as mainly a mono-ADP-ribosyltransferase, recently has shown a robust deacylase activity in addition to the already accepted substrate-dependent lipoamidase and deacetylase properties.

RATIONALE: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes.
OBJECTIVE: To investigate the role of α-ketoglutarate (αKG) in the epimetabolic control of DNA demethylation in CMSCs.

The epigenetic enzyme p300/CBP-associated factor (PCAF) belongs to the GCN5-related N-acetyltransferase (GNAT) family together with GCN5. Although its transcriptional and post-translational function is well characterized, little is known about its properties as regulator of cell metabolism. Here, we report the mitochondrial localization of PCAF conferred by an 85 aa mitochondrial targeting sequence (MTS) at the N-terminal region of the protein. In mitochondria, one of the PCAF targets is the isocitrate dehydrogenase 2 (IDH2) acetylated at lysine 180.

Background and aim: Plasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between ampli-cons.

Objective: In people living with HIV (PLWH), antiretroviral treatments have increased the median life expectancy. Raltegravir (RAL) represents a long-term safe regimen used both in the first-line antiretroviral treatments and in the optimization strategies. Aim of the study was to evaluate the real-life efficacy, tolerability, and safety of the long-term RAL use in a multicenter cohort of elderly PLWH.Methods: A 60-month follow-up observational study was carried out in the RAL-AGE Cohort including aged PLWH (≥60 years old) treated with RAL-based regimens (n = 96).

Formestane (4-hydroxyandrost-4-ene-3,17-dione, 4OH-AED) is an aromatase inhibitor prohibited in sports. In recent years, it has been demonstrated that it can also originate endogenously by the hydroxylation in C4 position of androstenedione. Thus, the use of isotope ratio mass spectrometry (IRMS) is mandatory according to the World Antidoping Agency (WADA) to discriminate endogenous from synthetic origin.