Rab1 interacts with GOLPH3 and controls Golgi structure and contractile ring constriction during cytokinesis in Drosophila melanogaster

Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster. We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks. Analysis by transmission electron microscopy and 3D-SIM super-resolution microscopy reveals loss of normal Golgi architecture in omt mutant spermatocytes indicating a role for Rab1 in Golgi formation. In dividing cells, Rab1 enables stabilization and contraction of actomyosin rings. We further demonstrate that GTP-bound Rab1 directly interacts with GOLPH3 and controls its localization at the Golgi and at the cleavage site. We propose that Rab1, by associating with GOLPH3, controls membrane trafficking and contractile ring constriction during cytokinesis

Vitamin C Deficiency in Patients With Acute Myeloid Leukemia

Vitamin C has been shown to play a significant role in suppressing progression of leukemia through epigenetic mechanisms. We aimed to study the role of vitamin C in acute myeloid leukemia (AML) biology and clinical course. To this purpose, the plasma levels of vitamin C at diagnosis in 62 patients with AML (including 5 cases with acute promyelocytic leukemia, APL),7 with myelodysplastic syndrome (MDS), and in 15 healthy donors (HDs) were studied. As controls, vitamins A and E levels were analysed. Expression of the main vitamin C transporters and of the TET2 enzyme were investigated by a specific RQ-PCR while cytoplasmic vitamin C concentration and its uptake were studied in mononuclear cells (MNCs), lymphocytes and blast cells purified from AML samples, and MNCs isolated from HDs. There were no significant differences in vitamin A and E serum levels between patients and HDs. Conversely, vitamin C concentration was significantly lower in AML as compared to HDs (p<0.0001), inversely correlated with peripheral blast-counts (p=0.029), significantly increased at the time of complete remission (CR) (p=0.04) and further decreased in resistant disease (p=0.002). Expression of the main vitamin C transporters SLC23A2, SLC2A1 and SLC2A3 was also significantly reduced in AML compared to HDs. In this line, cytoplasmic vitamin C levels were also significantly lower in AML-MNCs versus HDs, and in sorted blasts compared to normal lymphocytes in individual patients. No association was found between vitamin C plasma levels and the mutation profile of AML patients, as well as when considering cytogenetics or 2017 ELN risk stratification groups. Finally, vitamin C levels did not play a predictive role for overall or relapse-free survival. In conclusion, our study shows that vitamin C levels are significantly decreased in patients with AML at the time of initial diagnosis, further decrease during disease progression and return to normal upon achievement of CR. Correspondingly, low intracellular levels may mirror increased vitamin C metabolic consumption in proliferating AML cells

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

La valutazione dell'esposizione a metalli pesanti aerodispersi in ambienti non industriali: quale criterio seguire?

Numerose osservazioni, anche riportate dagli autori nel presente lavoro, hanno evidenziato la presenza di metalli pesanti nelle polveri aerodisperse in ambienti di vita (indoor e outdoor) o di lavoro non industriali, grazie anche alle tecniche analitiche oramai disponibili diffusamente. Si pone pertanto il problema della valutazione di tali esposizioni, professionali e non, anche a seguito di segnalazioni di effetti sulla salute. Il problema non è di facile approccio e risoluzione, in considerazione delle difficoltà di definire un valore di fondo per le concentrazioni di questi metalli, necessario come termine di paragone qualora si parli di effetti cancerogeni o di sensibilizzazione. Anche il problema dell’origine antropica o meno di tali contaminanti aggiunge ulteriore complessità alla questione, con conseguenti ricadute sulle indicazioni procedurali che dovrebbero essere ricavate per datori di lavoro, lavoratori, organi di controllo e popolazione in generale. Non ultimo, la definizione del problema potrebbe portare alla stesura di linee guida operative che indichino perlomeno un obbiettivo comune e condiviso

Influence of lipid composition on the ability of liposome loaded voacamine to improve the reversion of doxorubicin resistant osteosarcoma cells

The plant alkaloid voacamine (VOA) displays many interesting pharmacological activities thus, considering its scarce solubility in water, its encapsulation into liposome formulations for its delivery is an important goal. Different cationic liposome formulations containing a phospholipid, cholesterol and one of two diasteromeric cationic surfactants resulted able to maintain a stable transmembrane difference in ammonium sulfate concentration and/or pH gradient and to accumulate VOA in their internal aqueous bulk. The fluidity of the lipid bilayer affects both the ability to maintain a stable imbalance of protons and/or ammonium ions across the membrane and the entrapment efficiency. It was shown that VOA loaded into liposomes is more efficient than the free alkaloid to revert resistance of osteosarcoma cells resistant to doxorubicin to an extent depending on their composition. © 2019 Elsevier B.V

Glucosylated liposomes as drug delivery systems of usnic acid to address bacterial infections

Because of the increased incidence of infections caused by resistant pathogens, due to the intensive use of antibiotics, there is an urgent need to develop new therapeutic strategies against bacteria, possibly based on non conventional drugs. (+)-Usnic acid is a natural compound that exerts a potent antibacterial activity, however its clinical application is hampered by its scarce solubility in water. Usnic acid was included, by both passive and active loading techniques, in liposomes containing structurally related glucosylated amphiphiles. Liposome formulations were characterized from the physicochemical point of view and their activity against biofilm associated Staphylococcus epidermidis was also evaluated. The inclusion of usnic acid in glucosylated cationic liposomes promotes its penetration in biofilm matrix with a consequent increase of its antimicrobial activity. The effect of both cationic charge and sugar residue seems to be synergistic

Homogeneous and stable (+)-usnic acid loaded liposomes prepared by compressed CO2

The administration of hydrophobic actives and drugs for medical or cosmetical purposes generally requires a formulation that ensures adequate water solubility, which can be achieved through the encapsulation in liposomes. For the vehiculation of (+)-usnic acid (UA), a hydrophobic compound with antioxidant activity, we have prepared liposomes in a one-step process using compressed CO2. The investigated formulations are mainly composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and cholesterol, but contain also a small molar fraction (10%) of a synthetic surfactant derived from L-prolinol. In previous investigations liposomes containing L-prolinol derivatives showed a higher efficacy as DNA or drug delivery systems with respect to liposomes of mere phospholipids. As a consequence, they were added to liposomes to make them more suitable UA delivery systems. By testing different surfactant chain lengths and headgroups, we studied how the chemical nature of the surfactant affects the physicochemical vesicle properties and their interaction with UA. Most formulations, especially those containing surfactants with longer alkyl chains (C14 and C16), show a good potentiality as UA delivery systems because they exhibit a higher stability, vesicle-to-vesicle homogeneity and bilayer compaction with respect to analog liposomes prepared by the conventional thin film hydration previously investigated. Our results confirm the advantages of DELOS-SUSP also in the case of mixed liposomes containing phospholipids and synthetic ionic surfactants. Moreover, this study demonstrates that liposomes composed of the same lipids can feature different properties if prepared according to different methodologies. In addition, this investigation points out that also the properties that a solute included in the bilayer show can be affected by the technique used for liposomes preparation.This work was financially supported by the Ministry of Economy, Industry and Competitiveness of Spain through the “MOTHER” project (MAT2016-80826-R). Furthermore, the research leading to these results has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement N° 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia. The preparation of liposomes and their characterization were performed by the ICTS “NANBIOSIS”, more specifically by the Biomaterial Processing and Nanostructuring Unit (U6), Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) located at the Institute of Materials Science of Barcelona (ICMAB-CSIC)Peer reviewe