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This study investigated the performance of 24 commercial disinfectants present on the market during last year according to the manufacturer’s instructions. Recently, national and international organizations of public health performed studies on disinfection products due to the increasing awareness of the potential and growing risks on human health, such as skin damage and reactions in the mucosal lining, especially for the healthcare workers in their frequent daily use. However, there are many limitations in the common cleaning/disinfection products on market as in the selection of effective disinfectants to decontaminate inanimate surfaces. We analyzed the disinfection power of hydrogen peroxide, quaternary ammonium compounds, alcohols, phenols and aldehydes used as active principles according to international guidelines. The antimicrobial properties were assessed by broth microdilution, and antibiofilm properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus); their virucidal efficacy was tested against Herpes simplex virus type 1 (HSV-1) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quaternary ammonium compounds demonstrated better efficacy than others and in some cases ready to use products had also virucidal and antimicrobial activities after dilution at 0.125%. The scientific evidence indicates that many commercial products are used at high concentrations and high doses and this could have deleterious effects both on human health and the environment. A lower concentration of active ingredients would avoid the excessive release of chemicals into the environment and improve skin tolerance, ensuring the health and safety protection of workers, including the healthcare operators at their workplace.

International audience; The knowledge of the mechanism used by vectors to gain access to cell interiors is key to the development of effective drug delivery tools for different pathologies. The role of the initial interaction with the membrane bilayer is widely recognized, although not fully understood. We use neutron reflectivity experiments and internalization studies with cells to reveal the extent of interaction of dendrimers functionalized with the peptide gH625 with biomimetic membranes. We further investigate the internalization by use of Caco-2 cells for assessing the membrane permeability properties of the peptide-dendrimer construct. Neutron reflectivity allowed for the hypothesis that the peptide-dendrimer is able to pass across the bilayer which was confirmed via permeability studies. We find that gH625-dendrimers interact more strongly with cholesterol containing membranes. The advances in our understanding of the mechanism of drug uptake are extremely useful to push further the design of new drug delivery systems

Antimicrobial peptides, such as bovine lactoferrin (bLF), are produced by a wide variety of organisms. AMPs represent a first line defence against invading microbes and are found in large quantity in several secretory fluids [1] . They are relatively short, amphiphilic and positively charged. bLF is an 80- kDa iron-binding, multifunctional cationic glycoprotein of the transferrin family. This protein is active against a widespread range of microbiological organisms: bacteria, viruses, fungi and parasites [2,3,4]. In order to obtain novel active peptides from bLF, several approaches have been used. Two novel active peptides have been identified in our study. In agreement with the not disclosure agreement for the pending patent N°102015000044047*, we are not allowed to report the sequences in the abstract. These peptides, named respectively KFp and LKp, were synthesized using the standard solid-phase- 9-fluorenylmethoxycarbonyl (Fmoc) method. Antibacterial activity of KFp and LKp was analyzed by minimal inhibitory concentration (MIC) using the broth microdilution method outlined by the Clinical and Laboratory StandardsInstitute (CLSI) on two bacteria strains: Escherichia coli ATCC 11229 and Staphylococcus aureus ATCC 6538. Likewise, the antiviral activity was performed on HSV-1using a co-treatment assay. Moreover, their cytotoxicity activity was evaluated by the MTT assay.According to the study conducted, these novel peptides show a marked broad-spectrum antimicrobial and antiviral activity with a low toxicity. This can be a favorable prerequisite for the developing and for the use of these peptides in vivo, as additional therapeutic agents and/or as alternative to the conventional antibiotics.

The advent of nanotechnology brought the promise to revolutionize disease treatment. In recent years, nanotechnology has been successfully utilized to create novel drug delivery systems, which allow the reduction of unwanted side effects of systemic delivery, while increasing drug accumulation in specific cells of the body and improving the therapeutic efficacy. The knowledge of the mechanism used by vectors to gain access into the cell interior is key to the development of novel and effective drug delivery tools to apply for many different pathologies. Dendrimers have been used as powerful platforms for drug delivery. They are perfectly hyperbranched macromolecules with a well-defined structure, which exhibit properties very different from linear polymers with the same composition and molecular weight. The attachment of the peptide sequences to the termini of a dendrimer allows the conjugate to penetrate into the cellular matrix, whereas the unfunctionalized dendrimer is excluded from translocation. The peptide functionalized dendrimer is rapidly taken into the cells mainly through a non-active translocation mechanism[1-2]. The role of the initial interaction with the membrane bilayer is widely accepted, although it is still unclear. We used neutron reflectivity experiments and internalization studies with cells to reveal the extension of interaction of dendrimers functionalized with the peptide gH625 with biomimetic membranes. gH625 represents a good choice for the design of promising carriers to deliver drugs for the treatment of human diseases, while the goal of the internalization studies was to investigate the use of Caco2 cells as a possible tool for assessing the membrane permeability properties of the peptido-dendrimer. The study has demonstrated that dendrimer functionalized with gH625 is promising for the drug delivery.

Background and AIM Hepatocellular carcinoma (HCC) is a frequent complication of HCV liver cirrhosis. The reduction of risk after the clearance of HCV-RNA is debated. The aim of our study was to detect the appearance of HCC during the follow-up after antiviral treatment with direct acting antiviral therapy.Patients and Methods: In four specialist Centers, 280 HCV patients were analyzed. The choice of the regimen was based on genotype and stage of liver disease. Abdomen ultrasonography was performed prior, at the end of therapy, and after six months. Biochemistry, BMI, presence of comorbidity, and any complications of related to cirrhosis were also evaluated.Results: Nine HCC were found by ultrasonography (5 cases at the end of therapy, 4 cases 3 months after the end of follow-up); in all cases, HCC was confirmed by a second level imaging examination (computed tomography or magnetic resonance). Characteristics of patients were: male (66.9%; range 56-77), BMI (median 25.4; range 21-40). Prevalence of diabetes was 55.2%. Genotypes were: 1b (6 patients), 1a (2 patients), 2a/2c (1 patient). The therapies were: sofosbuvir plus simeprevir (1 patient), sofosbuvir plus simeprevir plus ribavirin (2 patients), sofosbuvir plus daclatasvir plus ribavirin (2 patients), sofosbuvir plus ribavirin (2 patients), Viekirax + Exviera plus ribavirin (2 patient). One patient only experienced a viral relapse at week 12 after the end of therapy. The incidence of HCC was 3.2%.Conclusions: In patients with liver cirrhosis, even if HCV replication stops, a close follow-up with ultrasonography is mandatory. Since the cumulative incidence is high, a greater sample size is necessary to clarify if the interferon-free antiviral therapy had an influence on the onset of HCC.

Estrogen receptor alpha (ERalpha) is a modular protein of the steroid/nuclear receptor family of transcriptional regulators that upon binding to the hormone undergoes structural changes, resulting in its nuclear translocation and docking to specific chromatin sites. In the nucleus, ERalpha assembles in multiprotein complexes that act as final effectors of estrogen signaling to the genome through chromatin remodeling and epigenetic modifications, leading to dynamic and coordinated regulation of hormone-responsive genes. Identification of the molecular partners of ERalpha and understanding their combinatory interactions within functional complexes is a prerequisite to define the molecular basis of estrogen control of cell functions. To this end, affinity purification was applied to map and characterize the ERalpha interactome in hormone-responsive human breast cancer cell nuclei. MCF-7 cell clones expressing human ERalpha fused to a tandem affinity purification tag were generated and used to purify native nuclear ER-containing complexes by IgG-Sepharose affinity chromatography and glycerol gradient centrifugation. Purified complexes were analyzed by two-dimensional DIGE and mass spectrometry, leading to the identification of a ligand-dependent multiprotein complex comprising beta-actin, myosins, and several proteins involved in actin filament organization and dynamics and/or known to participate in actin-mediated regulation of gene transcription, chromatin dynamics, and ribosome biogenesis. Time course analyses indicated that complexes containing ERalpha and actin are assembled in the nucleus early after receptor activation by ligands, and gene knockdown experiments showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for assembly and/or stability of these complexes. Based on these results, we propose that the actin network plays a role in nuclear ERalpha actions in breast cancer cells, including coordinated regulation of target gene activity, spatial and functional reorganization of chromatin, and ribosome biogenesis.

The family of histone deacetylases (HDACs) has recently emerged as important drug targets for treatment of slow progressive neurodegenerative disorders, including Huntington's disease (HD). Broad pharmaceutical inhibition of HDACs has shown neuroprotective effects in various HD models. Here we examined the susceptibility of HDAC targets for drug treatment in affected brain areas during HD progression. We observed increased HDAC1 and decreased HDAC4, 5 and 6 levels, correlating with disease progression, in cortices and striata of HD R6/2 mice. However, there were no significant changes in HDAC protein levels, assessed in an age-dependent manner, in HD knock-in CAG140 mice and we did not observe significant changes in HDAC1 levels in human HD brains. We further assessed acetylation levels of α-tubulin, as a biomarker of HDAC6 activity, and found it unchanged in cortices from R6/2, knock-in, and human subjects at all disease stages. Inhibition of deacetylase activities was identical in cortical extracts from R6/2 and wild-type mice treated with a class II-selective HDAC inhibitor. Lastly, treatment with class I- and II-selective HDAC inhibitors showed similar responses in HD and wild-type rat striatal cells. In conclusion, our results show that class I and class II HDAC targets are present and accessible for chronic drug treatment during HD progression and provide impetus for therapeutic development of brain-permeable class- or isoform-selective inhibitors.