Analysis of the utility of a rapid vesicle isolation method for clinical strains of .

, a pathogen capable of causing diseases ranging from mild to life-threatening, has a large arsenal of virulence factors. Notably, extracellular vesicles have emerged as significant players in the pathogenesis of this organism. However, the full range of their functions is still being studied, and difficulties related to vesicle purification (long protocols, low yields, and specialized instruments) have become a major obstacle for their characterization.

Are periodontitis and psoriasis associated? A pre-clinical murine model.

Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models.

Materials And Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death.

In Vivo Efficacy and Toxicity of an Antimicrobial Peptide in a Model of Endotoxin-Induced Pulmonary Inflammation.

SET-M33 is a synthetic peptide that is being developed as a new antibiotic against major Gram-negative bacteria. Here we report two in vivo studies to assess the toxicity and efficacy of the peptide in a murine model of pulmonary inflammation. First, we present the toxicity study in which SET-M33 was administered to CD-1 mice by snout inhalation exposure for 1 h/day for 7 days at doses of 5 and 20 mg/kg/day.

Extracellular Vesicles of : Friends and Foes.

Extracellular vesicles (Evs) are small spherical vesicles capable of transporting molecules (such as proteins, nucleic acids and lipids) from one cell to another. They have been implicated in processes such as cell-to-cell communication, pathogenicity, biofilm formation and metabolism. In parallel, Evs have been proposed as interesting biotechnological tools.

Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo.

Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol.

Safety evaluations of a synthetic antimicrobial peptide administered intravenously in rats and dogs.

The antimicrobial peptide SET-M33 is under study for the development of a new antibiotic against major Gram-negative pathogens. Here we report the toxicological evaluation of SET-M33 administered intravenously to rats and dogs. Dose range finding experiments determined the doses to use in toxicokinetic evaluation, clinical biochemistry analysis, necroscopy and in neurological and respiratory measurements.

Antimicrobial Peptides Active in In Vitro Models of Endodontic Bacterial Infections Modulate Inflammation in Human Cardiac Fibroblasts.

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local.

A MEG compatible, interactive IR game paradigm for the study of visuomotor reach-to-target movements in young children and clinical populations: The Target-Touch Motor Task.

Background: The conventional focus on discrete finger movements (i.e., index finger flexion or button-box key presses) has been an effective method to study neuromotor control using magnetoencephalography (MEG).

Analysis of 6YO pediatric human body model kinematics and kinetics to determine submarining across naturalistic seating postures.

Objectives: The aim of this study was to analyze the kinematics and kinetics of a naturalistically seated 6-year-old (6YO) pediatric human body model and evaluate the metrics described by earlier studies for pediatric ATDs to indicate whether different postures and booster seats were more associated with submarining than others in a frontal impact.

Methods: The PIPER 6YO pediatric human body model was restrained on a lowback (LBB) and a highback (HBB) booster child restraint seat (CRS) in four naturalistic seating postures: leaning-forward, leaning-inboard, leaning-outboard, and a pre-submarining posture, and a baseline reference seating position as per the FMVSS No. 213 protocol.

The Influence of Short Motifs on the Anticancer Activity of HB43 Peptide.

Despite the remarkable similarity in amino acid composition, many anticancer peptides (ACPs) display significant differences in terms of activity. This strongly suggests that particular relative dispositions of amino acids (motifs) play a role in the interaction with their biological target, which is often the cell membrane. To better verify this hypothesis, we intentionally modify HB43, an ACP active against a wide variety of cancers.

Expression and Role of Heparan Sulfated Proteoglycans in Pancreatic Cancer.

Pancreatic cancer is a lethal condition with poor outcomes and an increasing incidence. The unfavourable prognosis is due to the lack of early symptoms and consequent late diagnosis. An effective method for the early diagnosis of pancreatic cancer is therefore sought by many researchers in the field.

Analysis of Kinematic Response of Pediatric Occupants Seated in Naturalistic Positions in Simulated Frontal Small Offset Impacts: With and Without Automatic Emergency Braking.

Naturalistic driving studies have shown that pediatric occupants do not assume ideal seating positions in real-world scenarios. Current vehicle assessment programs and child restraint system (CRS) sled tests, such as FMVSS No. 213, do not account for a wide range of seating postures that are typically observed during real-world trips.

Heparan Sulfate Proteoglycans Can Promote Opposite Effects on Adhesion and Directional Migration of Different Cancer Cells.

Heparan sulfate proteoglycans take part in crucial events of cancer progression, such as epithelial-mesenchymal transition, cell migration, and cell invasion. Through sulfated groups on their glycosaminoglycan chains, heparan sulfate proteoglycans interact with growth factors, morphogens, chemokines, and extracellular matrix (ECM) proteins. The amount and position of sulfated groups are highly variable, thus allowing differentiated ligand binding and activity of heparan sulfate proteoglycans.

Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids.

The peptide SET-M33 is a molecule synthesized in tetra-branched form which is being developed as a new antibiotic against Gram-negative bacteria. Its isomeric form with D amino acids instead of the L version (SET-M33D) is also able to kill Gram-positive bacteria because of its higher resistance to bacterial proteases (Falciani et al., , 2012, 7, e46259).

Endocytosis and Trafficking of Heparan Sulfate Proteoglycans in Triple-Negative Breast Cancer Cells Unraveled with a Polycationic Peptide.

The process of heparan sulfate proteoglycan (HSPG) internalization has been described as following different pathways. The tumor-specific branched NT4 peptide has been demonstrated to bind HSPGs on the plasma membrane and to be internalized in tumor cell lines. The polycationic peptide has been also shown to impair migration of different cancer cell lines in 2D and 3D models.

Pediatric occupant human body model kinematic and kinetic response variation to changes in seating posture in simulated frontal impacts - with and without automatic emergency braking.

Objective: The study quantifies the kinematics of children in booster child restraint systems (CRSs) in various naturalistic seating postures exposed to frontal impacts in a full-vehicle environment, with and without the application of pre-crash automatic emergency braking.

Methods: The PIPER 6YO and 10YO pediatric human body models were positioned in CRSs. The 6YO was restrained on a lowback (LBB) and highback (HBB) booster, while the 10YO was positioned on an LBB and in a NoCRS condition.

Molecular definition of the interaction between a tumor-specific tetrabranched peptide and LRP6 receptor.

The tumor-specific tetrabranched peptide NT4 binds membrane sulfate glycosaminoglycans and receptors belonging to the low density lipoprotein receptor-related protein (LRP) family, like LRP6, which are overexpressed in cancer. The binding occurs through a multimeric positively-charged motif of NT4 that interacts with negatively charged motives in both glycosaminoglycans and LRP receptors. LRP6 has an essential function in canonical Wnt signaling, acting together with receptors of the Frizzled family as coreceptor for Wnt ligands.

A New NT4 Peptide-Based Drug Delivery System for Cancer Treatment.

The development of selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetrabranched peptide known as NT4, which is a promising cancer theranostic by virtue of its high cancer selectivity. We developed NT4 directly conjugated with one, two, or three units of paclitaxel and an NT4-based nanosystem, using NIR-emitting quantum dots, loaded with the NT4 tumor-targeting agent and conjugated with paclitaxel, to obtain a NT4-QD-PTX nanodevice designed to simultaneously detect and kill tumor cells.

Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Infections.

Introduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action.

An antimicrobial molecule mitigates signs of sepsis in vivo and eradicates infections from lung tissue.

The peptide sequence KKIRVRLSA was synthesized in a dimeric structure (SET-M33DIM) and evaluated as a candidate drug for infections due to multidrug-resistant (MDR) Gram-negative pathogens. SET-M33DIM showed significant antibacterial activity against MDR strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli (Minimal Inhibitory Concentration [MICs], 1.5-11 µM), and less activity against Pseudomonas aeruginosa (MICs, 11-22 µM).

NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide.

The synthetic antimicrobial peptide SET-M33 is being developed as a possible new antibacterial candidate for the treatment of multi-drug resistant bacteria. SET-M33 is a branched peptide featuring higher resistance and bioavailability than its linear analogues. SET-M33 shows antimicrobial activity against different species of multi-resistant Gram-negative bacteria, including clinically isolated strains of , , and .

In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection.

Due to the increasing need of new treatment options against bacterial lung infections, novel antimicrobial peptides (AMPs) are under development. Local bioavailability and less systemic exposure lead to the inhalation route of administration. Combining AMPs with nanocarriers (NCs) into nanosystems (NSs) might be a technique for improved results.

Unraveling Heparan Sulfate Proteoglycan Binding Motif for Cancer Cell Selectivity.

Membrane heparan sulfate proteoglycans (HSPG) regulate cell proliferation, migration, and differentiation and are therefore considered key players in cancer cell development processes. Here, we used the NT4 peptide to investigate how the sulfation pattern of HSPG on cells drives binding specificity. NT4 is a branched peptide that binds the glycosaminoglycan (GAG) chains of HSPG.