10 research outputs found

    The acetyltransferase p300 is recruited in trans to multiple enhancer sites by lncSmad7

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    The histone acetyltransferase p300 (also known as KAT3B) is a general transcriptional coactivator that introduces the H3K27ac mark on enhancers triggering their activation and gene transcription. Genome-wide screenings demonstrated that a large fraction of long non-coding RNAs (lncRNAs) plays a role in cellular processes and organ development although the underlying molecular mechanisms remain largely unclear (1,2). We found 122 lncRNAs that interacts directly with p300. In depth analysis of one of these, lncSmad7, is required to maintain ESC self-renewal and it interacts to the C-terminal domain of p300. lncSmad7 also contains predicted RNA-DNA Hoogsteen forming base pairing. Combined Chromatin Isolation by RNA precipitation followed by sequencing (ChIRP-seq) together with CRISPR/Cas9 mutagenesis of the target sites demonstrate that lncSmad7 binds and recruits p300 to enhancers in trans, to trigger enhancer acetylation and transcriptional activation of its target genes. Thus, these results unveil a new mechanism by which p300 is recruited to the genome

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

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    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

    Molecularly Imprinted Microrods via Mesophase Polymerization

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    The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via “mesophase polymerization”. The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology

    Mesoporous nanocrystalline TiO2 loaded with ferulic acid for sunscreen and photo-protection: safety and efficacy assessment

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    In the present study, the use of surfactant-free mesoporous TiO2 combined with an antioxidant and photoprotecting agent, such as ferulic acid (FA), as a sunscreen was investigated for the first time. Ferulic acid is a natural antioxidant characterized by UV absorption capacity and radical scavenging activities and, due to these properties, it has been approved as an active ingredient in several skin lotions and sunscreens. However, despite the double function exerted by FA, the use of this molecule in the cosmetic field is limited by its poor stability. Aiming to overcome this drawback, mesoporous TiO2, prepared by using a sol-gel route assisted by a polyoxyethylene-polyoxypropylene block copolymer template followed by solvothermal treatment, was used as a matrix for the encapsulation of ferulic acid. The stability studies performed confirmed the ability of the prepared material to preserve the active molecule from degradation induced by light and, therefore, its properties. Antioxidant and anti-inflammatory activities of FA-loaded titania (TiO2@FA) and titania matrix (TiO2) were evaluated and high scavenging activity towards DPPH, ABTS and NO radicals were recorded. The in vitro assessment of the spectrophotometric Sun Protection Factor (SPF) was also performed and a value of 14.7 was observed for TiO2@FA while mesoporous TiO2 showed a lower SPF value equal to 2.6. These results suggested the potential application of the titania-doped FA as a "booster of SPF" that is able to enhance the SPF of a sunscreen. Furthermore, in vitro safety studies confirmed the biocompatibility of the prepared material and the absence of skin irritation

    Interconnected PolymerS TeChnology (IPSTiC): An Effective Approach for the Modulation of 5α-Reductase Activity in Hair Loss Conditions

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    Hair loss represents a condition that adversely affects the social life of patients. The most common cause is androgenetic alopecia (AGA), which is a genetically determined progressive hair-loss condition involving 5α-reductase. In this study, a novel anti-baldness agent based on Interconnected PolymerS TeChnology (IPSTiC), which is an effective strategy for the delivery of bioactive molecules, was developed. This product (IPSTiC patch hair) is based on a polymeric blend consisting of high molecular weight hyaluronic acid and soybean proteins and is able to improve efficacy and stability of bioactive ingredients such as Origanum vulgare leaf extract, Camellia Sinensis leaf extract, and Capsicum Annuum fruit extract. The efficacy of the developed anti-baldness agent was investigated by performing several tests including NO radical and 5α-reductase inhibition assays, stability studies under different conditions, and in vitro diffusion studies using Franz cells. The biocompatibility of IPSTiC patch hair was also evaluated by in vitro analysis of the pro-sensitising potential and EPISKIN model. The obtained results confirmed both the efficacy and safety of IPSTiC patch hair supporting the potential use of this product in the topical treatment of AGA

    Biopolymeric self-assembled nanoparticles for enhanced antibacterial activity of Ag-based compounds

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    Microbial infections are still one of the major causes of death among world population. For this reason, there is an urgent need of new antimicrobial agents that express antibacterial activity. Silver-based compounds are known to be toxic against bacteria. One of the most representative examples is silver sulfadiazine. In our article we report the antibacterial activity of silver Nheterocyclic carbene complexes, tested againt a wide spectrum of microorganisms. MIC and MBC were calculated for each compound. We have also produced a dextran oleate conjugate, that was employed for the preparation of self-assembled biopolymeric nanoparticles

    Biopolymeric self-assembled nanoparticles for enhanced antibacterial activity of Ag-based compounds

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    Microbial infections still remain one of the main issues for human health. The rapid development of resistance towards the most common antimicrobial drugs in bacteria represents today a challenge in the infections management. In the present work we have investigated the antibacterial activity of a group of compounds, namely silver N-heterocyclic carbene complexes, against a broad spectrum of bacteria. For the most promising compound, a biopolymeric nanocarrier has been developed, in order to potentiate the metal complex activity against both Gram +ve and Gram −ve. The polymeric nanovehicle is based on dextran, modified with oleic acid residues, that confer amphiphilic properties to the polysaccharide. We have characterized the obtained biomaterial and studied its ability to self-assemble into nanoparticles in aqueous environment. Next, the transdermal diffusion analyses have been carried out to evaluate the ability of the polymeric particles to penetrate tissues. Thanks to the strategy adopted, we have fabricated an antibacterial system to which K. pneumoniae and E. coli are the most sensitive

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

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