Navigating Alzheimer's Disease Mouse Models: Age-Related Pathology and Cognitive Deficits.

Since the mid-1990s, scientists have been generating mouse models of Alzheimer's disease to elucidate key mechanisms underlying the onset and progression of the disease and aid in developing potential therapeutic approaches. The first successful mouse model of Alzheimer's disease was reported in 1995 with the generation of the PDAPP mice, which were obtained by the overexpression of gene coding for the amyloid precursor protein (APP). Since then, scientists have used different approaches to develop other APP overexpression mice, mice overexpressing tau, or a combination of them.

Impact of Nutrient Starvation on Biofilm Formation in : An Analysis of Growth, Adhesion, and Spatial Distribution.

This study investigates the impact of nutrient availability on the growth, adhesion, and biofilm formation of ATCC 27853 under static conditions. Bacterial behaviour was evaluated in nutrient-rich Luria-Bertani (LB) broth and nutrient-limited M9 media, specifically lacking carbon (M9-C), nitrogen (M9-N), or phosphorus (M9-P). Bacterial adhesion was analysed microscopically during the transition from reversible to irreversible attachment (up to 120 min) and during biofilm production/maturation stages (up to 72 h).

Generation of a Biotin-Tagged Dual-Display Phage.

Phage display is widely used in biomedical research. One of the great advantages of phage display is the specificity of the connection of a foreign peptide exposed outside the capsid to the intended target. Secondary detection systems, which are often laborious and costly, are required to identify and quantify the peptide/target interaction.

Multi-drug resistant Staphylococcus epidermidis from chronic wounds impair healing in human wound model.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S.

Anti-Biofilm Strategies: A Focused Review on Innovative Approaches.

Biofilm (BF) can give rise to systemic infections, prolonged hospitalization times, and, in the worst case, death. This review aims to provide an overview of recent strategies for the prevention and destruction of pathogenic BFs. First, the main phases of the life cycle of BF and maturation will be described to identify potential targets for anti-BF approaches.

Epigenetic Changes in Alzheimer's Disease: DNA Methylation and Histone Modification.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss, imposing a significant burden on affected individuals and their families. Despite the recent promising progress in therapeutic approaches, more needs to be done to understand the intricate molecular mechanisms underlying the development and progression of AD. Growing evidence points to epigenetic changes as playing a pivotal role in the pathogenesis of the disease.

Generation of a helper phage for the fluorescent detection of peptide-target interactions by dual-display phages.

Phage display is a molecular biology technique that allows the presentation of foreign peptides on the surface of bacteriophages. It is widely utilized for applications such as the discovery of biomarkers, the development of therapeutic antibodies, and the investigation of protein-protein interactions. When employing phages in diagnostic and therapeutic monitoring assays, it is essential to couple them with a detection system capable of revealing and quantifying the interaction between the peptide displayed on the phage capsid and the target of interest.

A Novel Serum-Based Diagnosis of Alzheimer's Disease Using an Advanced Phage-Based Biochip.

55 million people worldwide suffer from Alzheimer's disease (AD). A definitive diagnosis of AD is made postmortem after a neuropathological examination of the brain. There is an urgent need for an innovative, noninvasive methodology that allows for an early and reliable diagnosis.

Antimicrobial and Antibiofilm Photodynamic Action of Photosensitizing Nanoassemblies Based on Sulfobutylether-β-Cyclodextrin.

Developing new broad-spectrum antimicrobial strategies, as alternatives to antibiotics and being able to efficiently inactivate pathogens without inducing resistance, is one of the main objectives in public health. Antimicrobial photodynamic therapy (aPDT), based on the light-induced production of reactive oxygen species from photosensitizers (PS), is attracting growing interest in the context of infection treatment, also including biofilm destruction. Due to the limited photostability of free PS, delivery systems are increasingly needed in order to decrease PS photodegradation, thus improving the therapeutic efficacy, as well as to reduce collateral effects on unaffected tissues.

The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities.

Alzheimer's disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells.

Supramolecular assemblies based on polymeric cyclodextrin nanosponges and a cationic porphyrin with antimicrobial photodynamic therapy action.

Within of the increasing requirement of alternative approaches to fight emerging infections, nano-photosensitisers (nanoPS) are currently designed with the aim to optimize the antimicrobial photodynamic (aPDT) efficacy. The utilize of less expensive nanocarriers prepared by simple and eco-friendly methodologies and commercial photosensitisers are highly desiderable. In this direction, here we propose a novel nanoassembly composed of water soluble anionic polyester β-CD nanosponges (β-CD-PYRO hereafter named βNS) and the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4- yl)porphine (TMPyP).

Chronic wound microenvironment mediates selection of biofilm-forming multi drug resistant with capability to impair healing.

Venous leg ulcers (VLU) are the most common chronic wounds characterized by bacterial biofilms and perturbed microbiome. is primarily known as skin commensal beneficial for the host, however, some strains can form biofilms and cause infections. By employing shotgun metagenomic sequencing we show that genetic signatures of antimicrobial resistance, adhesion and biofilm formation in VLU isolates correlate with bacterial traits.

Applications of CRISPR-Cas9 in Alzheimer's Disease and Related Disorders.

Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease represent some of the most prevalent neurodegenerative disorders afflicting millions of people worldwide. Unfortunately, there is a lack of efficacious treatments to cure or stop the progression of these disorders. While the causes of such a lack of therapies can be attributed to various reasons, the disappointing results of recent clinical trials suggest the need for novel and innovative approaches.

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors.

The evolution of the SARS-CoV-2 virus during the COVID-19 pandemic was accompanied by the emergence of new heavily mutated viral variants with increased infectivity and/or resistance to detection by the human immune system. To respond to the urgent need for advanced methods and materials to empower a better understanding of the mechanisms of virus's adaptation to human host cells and to the immuno-resistant human population, we suggested using recombinant filamentous bacteriophages, displaying on their surface foreign peptides termed "mimotopes", which mimic the structure of viral receptor-binding sites on the viral spike protein and can serve as molecular probes in the evaluation of molecular mechanisms of virus infectivity. In opposition to spike-binding antibodies that are commonly used in studying the interaction of the ACE2 receptor with SARS-CoV-2 variants in vitro, phage spike mimotopes targeted to other cellular receptors would allow discovery of their role in viral infection in vivo using cell culture, tissue, organs, or the whole organism.

Role of Phage Capsid in the Resistance to UV-C Radiations.

The conformational variation of the viral capsid structure plays an essential role both for the environmental resistance and acid nuclear release during cellular infection. The aim of this study was to evaluate how capsid rearrangement in engineered phages of M13 protects viral DNA and peptide bonds from damage induced by UV-C radiation. From in silico 3D modelling analysis, two M13 engineered phage clones, namely P9b and 12III1, were chosen for (i) chemical features of amino acids sequences, (ii) rearrangements in the secondary structure of their pVIII proteins and (iii) in turn the interactions involved in phage capsid.

Effects of Heavy Ion Particle Irradiation on Spore Germination of spp. from Extremely Hot and Cold Environments.

Extremophiles are optimal models in experimentally addressing questions about the effects of cosmic radiation on biological systems. The resistance to high charge energy (HZE) particles, and helium (He) ions and iron (Fe) ions (LET at 2.2 and 200 keV/µm, respectively, until 1000 Gy), of spores from two thermophiles, SBP3 and T14, and two psychrotolerants, sp.

Sulfobutylether-β-cyclodextrin/5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine nanoassemblies with sustained antimicrobial phototherapeutic action.

Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT.

Regulation of filamentation by bacteria and its impact on the productivity of compounds in biotechnological processes.

The bacteria wall fulfills important physiological functions at the cell, depending on its composition and organization. Many researches focused their studies in understanding the change of its properties not only in strength and permeability, but also in morphological plasticity due to both chemical and physical stresses. In particular, filamentation morphology is a cryptic phenomenon, with involve for great variety of bacteria, which allow them to acquire adaptive benefits.

Innovative IgG Biomarkers Based on Phage Display Microbial Amyloid Mimotope for State and Stage Diagnosis in Alzheimer's Disease.

An innovative approach to identify new conformational antigens of Aβ recognized by IgG autoantibodies as biomarkers of state and stage in Alzheimer's disease (AD) patients is described. In particular, through the use of bioinformatics modeling, conformational similarities between several Aβ forms and other amyloid-like proteins with F1 capsular antigen (Caf1) of were first found. pVIII M13 phage display libraries were then screened against YPF19, anti-Caf1 monoclonal antibody, and IgGs of AD patients, in alternate biopanning cycles of a so-called "double binding" selection.

Bacteriophage Based Biosensors: Trends, Outcomes and Challenges.

Foodborne pathogens are one of the main concerns in public health, which can have a serious impact on community health and health care systems. Contamination of foods by bacterial pathogens (such as , , , results in human infection. A typical example is the current issue with Coronavirus, which has the potential for foodborne transmission and ruling out such concerns is often difficult.

Evolution of a Landscape Phage Library in a Mouse Xenograft Model of Human Breast Cancer.

Peptide-displayed phage libraries are billion-clone collections of diverse chimeric bacteriophage particles, decorated by genetically fused peptides built from a random combination of natural amino acids. Studying the molecular evolution of peptide-displayed libraries in mammalian model systems, using in vivo phage display techniques, can provide invaluable knowledge about the underlying physiology of the vasculature system, allow recognition of organ- and tissue-specific networks of protein-protein interactions, and provide ligands for targeted diagnostics and therapeutics. Recently, we discovered that landscape phage libraries, a specific type of multivalent peptide phage display library, expose on their surface comprehensive collections of elementary binding units (EBUs), which can form short linear motifs (SLiMs) that interact with functional domains of physiologically relevant proteins.

Glutamine-induced filamentous cells of Pseudomonas mediterranea CFBP-5447T as producers of PHAs.

Polyhydroxyalkanoates (PHAs) are considerable biopolymers that have gained an increasing biotechnological interest in different applications, although their industrial production presents several limitations. Filamentous bacterial cells could represent a possible strategy to increase PHA yield, since more abundant PHA inclusions can be stored in elongated than in rod-shaped cells. At first, we determined the optimal batch culture conditions to induce filamentation in Pseudomonas mediterranea CFBP-5447T, using glutamine, glycerol, glucose, and sodium octanoate, as the sole carbon source, at low- (100 rpm) or high- (250 rpm) shaking speeds.

Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells-An Alternative Mechanism of Directed Molecular Evolution.

Low performance of actively targeted nanomedicines required revision of the traditional drug targeting paradigm and stimulated the development of novel phage-programmed, self-navigating drug delivery vehicles. In the proposed smart vehicles, targeting peptides, selected from phage libraries using traditional principles of affinity selection, are substituted for phage proteins discovered through combinatorial avidity selection. Here, we substantiate the potential of combinatorial avidity selection using landscape phage in the discovery of Short Linear Motifs (SLiMs) and their partner domains.

Bio-hybrid gold nanoparticles as SERS probe for rapid bacteria cell identification.

This study reports the utilization of engineered molecular networks between bacteriophage (or phage) and gold nanoparticles (AuNPs) prepared ablating a high purity gold target in water by nanosecond laser source. Gold colloids are assembled with P9b phage clone, displaying the specific peptide (QRKLAAKLT), able to bind P. aeruginosa.

Phage-based assay for rapid detection of bacterial pathogens in blood by Raman spectroscopy.

Sepsis is a systemic inflammatory response ensuing from presence and persistence of microorganisms in the bloodstream. The possibility to identify them at low concentrations may improve the problem of human health and therapeutic outcomes. So, sensitive and rapid diagnostic systems are essential to evaluate bacterial infections during the time, also reducing the cost.