GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in Triple Negative Breast Cancer

Dissemination of cancer cells from the primary tumors to distant organs represents the main cause of death in cancer patients. GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies including breast cancer where GTSE1 expression levels correlate with tumor grade, enhanced invasive potential and negative prognosis. Given the strong association between GTSE1 deregulation and bad clinical outcome the aim of this work was to clarify how GTSE1 is regulated in triple negative breast cancer and the molecular mechanism underlying GTSE1dependent cell movement. Here, I identified GTSE1 as a novel direct TEAD4 and E2F1 transcription factors target gene, highlighting a role for YAP and TAZ co-activators in GTSE1 transcriptional regulation. Frequently deregulated in cancers, TEAD4 and the co-activators YAP and TAZ have been reported to promote tumorigenesis, invasion and metastasis in breast cancer. I demonstrated that the effect of the TEAD transcription factor on cell migration and invasion is GTSE1-dependent. Moreover, I found that TEAD controls cell protrusions formation, required for cell migration, through GTSE1 protein, unveiling a relevant effector role for GTSE1 in the TEAD-dependent cellular functions

Application of Dendrimers for Treating Parasitic Diseases

Despite advances in medical knowledge, parasitic diseases remain a significant global health burden and their pharmacological treatment is often hampered by drug toxicity. Therefore, drug delivery systems may provide useful advantages when used in combination with conventional therapeutic compounds. Dendrimers are three-dimensional polymeric structures, characterized by a central core, branches and terminal functional groups. These nanostructures are known for their defined structure, great water solubility, biocompatibility and high encapsulation ability against a wide range of molecules. Furthermore, the high ratio between terminal groups and molecular volume render them a hopeful vector for drug delivery. These nanostructures offer several advantages compared to conventional drugs for the treatment of parasitic infection. Dendrimers deliver drugs to target sites with reduced dosage, solving side effects that occur with accepted marketed drugs. In recent years, extensive progress has been made towards the use of dendrimers for therapeutic, prophylactic and diagnostic purposes for the management of parasitic infections. The present review highlights the potential of several dendrimers in the management of parasitic diseases

First Italian outbreak of VIM-producing Serratia marcescens in an adult polyvalent intensive care unit, August-October 2018: A case report and literature review

Carbapenem-resistant Enterobacteriaceae has become a significant public health concern as hospital outbreaks are now being frequently reported and these organisms are becoming difficult to treat with the available antibiotics

The Intestinal Biofilm of Pseudomonas aeruginosa and Staphylococcus aureus Is Inhibited by Antimicrobial Peptides HBD-2 and HBD-3

Background: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections

Effects of Single α-to-β Residue Replacements on Recognition of an Extended Segment in a Viral Fusion Protein

Partial replacement of α-amino acid residues with β-amino acid residues has been established as a strategy for preserving target-engagement by helix-forming polypeptides while suppressing susceptibility to proteolysis. The impact of β-residue incorporation within polypeptides that adopt less regular conformations, however, has received less attention. The HRC domains of fusion glycoproteins from pathogenic paramyxoviruses contain a segment that must adopt an extended conformation in order to engage the HRN domain in the post-fusion state and drive merger of the viral envelope with a target cell membrane. Here we examine the impact of single α-to-β substi-tutions within this extended N-terminal segment of the engineered HRC peptide VIQKI. Stabilities of helix-bundles formed with a native viral HRN have been evaluated, the structures of five helix-bundles have been determined, and antiviral efficacies have been measured. Many sites within the extended segment show functional tolerance of α-to-β substitution. These results offer a basis for future develop-ment of protease-resistant inhibitors of paramyxovirus infection

Effects of single α-to-β residue replacements on recognition of an extended segment in a viral fusion protein

Partial replacement of α-amino acid residues with β-amino acid residues has been established as a strategy for preserving target-engagement by helix-forming polypeptides while altering other properties. The impact of β-residue incorporation within polypeptides that adopt less regular conformations, however, has received less attention. The HRC domains of fusion glycoproteins from pathogenic paramyxoviruses contain a segment that must adopt an extended conformation in order to co-assemble with the HRN domain in the post-fusion state and drive merger of the viral envelope with a target cell membrane. Here we examine the impact of single α-to-β substitutions within this extended N-terminal segment of an engineered HRC peptide designated VIQKI. Stabilities of hexameric co-assemblies formed with the native HPIV3 HRN have been evaluated, the structures of five co-assemblies have been determined, and antiviral efficacies have been measured. Many sites within the extended segment show functional tolerance of α-to-β substitution. These results offer a basis for future development of paramyxovirus infection inhibitors with novel biological activity profiles, possibly including resistance to proteolysis

Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives

According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies)

Grape Canes from Typical Cultivars of Campania (Southern Italy) as a Source of High-Value Bioactive Compounds: Phenolic Profile, Antioxidant and Antimicrobial Activities

The purpose of the current study was to determine the phenolic composition, antioxidant, and antimicrobial activities in grape cane extracts from typical cultivars of Southern Italy. Aqueous extracts at different pHs (1-13) were prepared from "Aglianico", "Fiano", and "Greco" grape canes. The results demonstrated that an alkaline pH (13.00) produced the best polyphenol-rich extracts, as the total phenolic content was more than double when compared to the respective extracts prepared at pH 1.00. "Greco" grape canes gave the highest quantity of phenolic compounds at each pH, ranging from 42.7 +/- 0.4 to 104.3 +/- 3.0 mg Gallic Acid Equivalents (GAE)/g Dry Extract (DE) from pH 1.00 to 13.00. The Radical Scavenging Activity (RSA) and the Ferric Reducing Antioxidant Power (FRAP) were measured. The highest antioxidant activity was showed by "Greco" extract at pH 7.00. Seventy-five compounds were identified in the extracts by HPLC-MS with six of them described for the first time in grape canes. Procyanidins were highly abundant in extracts at pH 7.00, whereas stilbenoids were the most represented compounds at pH 13.00. Very strong antiviral activity against herpes simplex viruses was recorded for the extracts at pH 7.00 and 13.00 that were active in the early stages of infection by acting directly against the viral particles. The overall results suggest that grape canes, currently underutilized, can be usefully valorised by providing active extracts to use as antioxidant and antiviral agents